<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medalphabet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский алфавит</journal-title><trans-title-group xml:lang="en"><trans-title>Medical alphabet</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2078-5631</issn><issn pub-type="epub">2949-2807</issn><publisher><publisher-name>ООО «Альфмед»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33667/2078-5631-2019-1-2(377)-35-42</article-id><article-id custom-type="elpub" pub-id-type="custom">medalphabet-945</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Статьи</subject></subj-group></article-categories><title-group><article-title>Новые стратегии диагностики и лечения болезни Альцгеймера: моноклональные антитела к бета-амилоиду</article-title><trans-title-group xml:lang="en"><trans-title>New strategies for diagnosis and treatment of Alzheimer's disease: monoclonal antibodies to beta-amyloid</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пилипович</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Pilipovich</surname><given-names>A. A.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Данилов</surname><given-names>А. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Danilov</surname><given-names>A. B.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГАОУ ВО «Первый Московский государственный медицинский университет имени И. М. Сеченова (Сеченовский университет)» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>First Moscow State Medical University n.a. I. M. Sechenov</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>19</day><month>01</month><year>2019</year></pub-date><volume>1</volume><issue>2</issue><issue-title>Неврология и психиатрия</issue-title><fpage>35</fpage><lpage>42</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Пилипович А.А., Данилов А.Б., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Пилипович А.А., Данилов А.Б.</copyright-holder><copyright-holder xml:lang="en">Pilipovich A.A., Danilov A.B.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.med-alphabet.com/jour/article/view/945">https://www.med-alphabet.com/jour/article/view/945</self-uri><abstract><p>Болезнь Альцгеймера (БА) - прогрессирующее нейродегенеративное заболевание, которое является наиболее распространенной причиной деменции. В настоящее время в мире насчитывается около 46,8 миллиона человек, страдающих БА. Считается, что число пациентов с БА удваивается почти каждые 20 лет, и все более остро стоит вопрос о своевременном лечении и продлении активной жизни данных пациентов. На сегодняшний день одобрены только пять препаратов для лечения БА, они включают ингибиторы холинэстеразы и антагонисты N-метилФ-аспартата рецепторов (мемантин). К сожалению, их применение обеспечивает временный и неполный симптоматический эффект, может сопровождаться побочными эффектами и не замедляет прогрессирование БА, поэтому крайне актуальна разработка лекарств для более эффективного лечения БА. Лабораторные и клинические исследования говорят о том, что в ближайшем будущем терапия БА станет более направленной на модификацию болезни и вероятно, что БА будет успешно лечиться еще до развития значительных когнитивных нарушений, на пресимптоматическом или доклиническом этапах. Главной терапевтической целью этих исследований является лечение патологического процесса (снижение β-амилоидоза или уменьшение образования нейрофибриллярных клубков) для предотвращения последующей нейродегенерации и возможного когнитивного снижения. В настоящее время, несмотря на всевозможные проблемы, иммунотерапия с введением моноклональных антител к β-амилоиду считается одним из наиболее перспективных подходов к уменьшению степени нейродегенерации.</p></abstract><trans-abstract xml:lang="en"><p>Alzheimer's disease (AD) is a progressive neurodegenerative disease that is the most common cause of dementia. Currently, there are about 46.8 million people with asthma in the world. It is believed that the number of patients with BA doubles almost every 20 years, and the issue of timely treatment and prolongation of the active life of these patients is becoming ever more acute. Nowdays only five drugs have been approved for the treatment of asthma, they include cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists (memantine). Unfortunately, their use provides tempora/y and incomplete symptomatic effect, can be accompanied by side effects and does not shw down the progression of asthma, therefore the development of drugs for more effective treatment of asthma is extremely important. Laboratory and clinical studies suggest that in the near future, AD-therapy will become more focused on disease modification and it is likely that AD will be successfully treated even before significant cognitive impairment develops, at the presymptom-atic or preclinical stages. The main therapeutic goal of these studies is the treatment of the pathological process (reduction of β-amyloidosis or reduction of the formation of neurofibrillaiy tangles) to prevent subsequent neurodegeneration and possible cognitive decline. Currently, despite all sorts of problems, immunotherapy with the introduction of monoclonal antibodies to β-amyloid is considered one of the most promising approaches to reducing the degree of neurodegeneration.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>болезнь Альцгеймера</kwd><kwd>нейродегенеративные заболевания</kwd><kwd>иммунотерапия</kwd><kwd>моноклональные антитела</kwd></kwd-group><kwd-group xml:lang="en"><kwd>β-амилоид</kwd><kwd>Alzheimer's disease</kwd><kwd>neurodegenerative diseases</kwd><kwd>immunotherapy</kwd><kwd>monoclonal antibodies</kwd><kwd>β-amyloid</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">АН G-С, Guerchet M, Wu Y-T, Prince M, Prina M. Chapter 2: The global prevalence of dementia. In: Prince M, GuerchetM, Ali G-C Wu Y-T, Prina M, editors. The Global Impact of Dementia. An analysis of prevalence, incidence, cost and trends. London: Alzheimer’s Disease international (ADI); 20І5. p. 10-29.</mixed-citation><mixed-citation xml:lang="en">АН G-С, Guerchet M, Wu Y-T, Prince M, Prina M. Chapter 2: The global prevalence of dementia. In: Prince M, GuerchetM, Ali G-C Wu Y-T, Prina M, editors. The Global Impact of Dementia. An analysis of prevalence, incidence, cost and trends. London: Alzheimer’s Disease international (ADI); 20І5. p. 10-29.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Xiaoguang Du, Xinyi Wang 1 and Meiyu Geng. Alzheimer’s disease hypothesis and related Therapies. Du et al. Translational Neurodegeneration. 2018; 7: 2.</mixed-citation><mixed-citation xml:lang="en">Xiaoguang Du, Xinyi Wang 1 and Meiyu Geng. Alzheimer’s disease hypothesis and related Therapies. Du et al. Translational Neurodegeneration. 2018; 7: 2.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Емелин А. Ю. Новые критерии диагностики болезни Альцгеймера. Неврология, нейропсихиатрия, психосоматика. 2011; 3 (4): 5-8.</mixed-citation><mixed-citation xml:lang="en">Емелин А. Ю. Новые критерии диагностики болезни Альцгеймера. Неврология, нейропсихиатрия, психосоматика. 2011; 3 (4): 5-8.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Sperling R. A., Aisen P.S., Beckett L. A., Bennett D. A., Craft S., Fagan A. M., Iwatsubo T., Jack C. R., Kaye J., Montine T. J., Park D. C., Reiman E. M., Rowe C. C., Siemer S. E., Stern Y., Yaffe K., Carrillo M. C., Thies B., Morrison-Bogorad M., Wagster M. V., Phelps C. H. Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimets Association workgroups on diagnostic guidelines for Alzheimer's disease Alzheimers Dement. 20ІІ; 7 (3): 280-292.</mixed-citation><mixed-citation xml:lang="en">Sperling R. A., Aisen P.S., Beckett L. A., Bennett D. A., Craft S., Fagan A. M., Iwatsubo T., Jack C. R., Kaye J., Montine T. J., Park D. C., Reiman E. M., Rowe C. C., Siemer S. E., Stern Y., Yaffe K., Carrillo M. C., Thies B., Morrison-Bogorad M., Wagster M. V., Phelps C. H. Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimets Association workgroups on diagnostic guidelines for Alzheimer's disease Alzheimers Dement. 20ІІ; 7 (3): 280-292.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992; 256 (5054): 184-185.</mixed-citation><mixed-citation xml:lang="en">Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992; 256 (5054): 184-185.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: time, space and ‘wingmen’. NatNeurosci. 2015; 18 (6): 800-806.</mixed-citation><mixed-citation xml:lang="en">Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: time, space and ‘wingmen’. NatNeurosci. 2015; 18 (6): 800-806.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease - insights from amyloidbeta metabolism beyond the brain. Nat Rev Neurol. 2017; 13 (10): 612-623.</mixed-citation><mixed-citation xml:lang="en">Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease - insights from amyloidbeta metabolism beyond the brain. Nat Rev Neurol. 2017; 13 (10): 612-623.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Bennett D. A., Schneider J.A., Arvanitakis Z., Kelly JF, Aggarwal NT, Shah RC, Wilson RS. Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 2006; 66 (12): 1837-1844.</mixed-citation><mixed-citation xml:lang="en">Bennett D. A., Schneider J.A., Arvanitakis Z., Kelly JF, Aggarwal NT, Shah RC, Wilson RS. Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 2006; 66 (12): 1837-1844.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Cummings J, Aisen PS, DuBois B, Frölich L, Jack CR Jr, Jones RW, Morris JC, Raskin J, Dowsett SA, Scheltens P. Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther. 2016; 8: 39.</mixed-citation><mixed-citation xml:lang="en">Cummings J, Aisen PS, DuBois B, Frölich L, Jack CR Jr, Jones RW, Morris JC, Raskin J, Dowsett SA, Scheltens P. Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther. 2016; 8: 39.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Vassar R, Citron M. Abeta-generating enzymes: recent advances in beta- and gamma-secretase research. Neuron. 2000; 27 (3): 419-22.</mixed-citation><mixed-citation xml:lang="en">Vassar R, Citron M. Abeta-generating enzymes: recent advances in beta- and gamma-secretase research. Neuron. 2000; 27 (3): 419-22.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M, Begthel H, Cozijnsen M, Robine S, Winton DJ, Radtke F, Clevers H. Notch/ gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 2005; 435 (7044): 959-963.</mixed-citation><mixed-citation xml:lang="en">van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M, Begthel H, Cozijnsen M, Robine S, Winton DJ, Radtke F, Clevers H. Notch/ gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 2005; 435 (7044): 959-963.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Olry A, Chastagner P, Israël A, Brou C. Generation and characterization of mutant cell lines defective in gamma-secretase processing of notch and amyloid precursor protein. J Biol Chem. 2005; 280 (31): 28564-71.</mixed-citation><mixed-citation xml:lang="en">Olry A, Chastagner P, Israël A, Brou C. Generation and characterization of mutant cell lines defective in gamma-secretase processing of notch and amyloid precursor protein. J Biol Chem. 2005; 280 (31): 28564-71.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Tarassishin L, Yin YI, Bassit B, Li YM. Processing of notch and amyloid precursor protein by gamma-secretase is spatially distinct. Proc Natl Acad Sci U S A. 2004; 101 (49): 17050-17055.</mixed-citation><mixed-citation xml:lang="en">Tarassishin L, Yin YI, Bassit B, Li YM. Processing of notch and amyloid precursor protein by gamma-secretase is spatially distinct. Proc Natl Acad Sci U S A. 2004; 101 (49): 17050-17055.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Klaver DW, Wilce MC, Cui H, Hung AC, Gasperini R, Foa L, Small DH. Is BACE 1 a suitable therapeutic target for the treatment of Alzheimer’s disease? Current strategies and future directions. Biol Chem. 2010; 391 (8): 849-59.</mixed-citation><mixed-citation xml:lang="en">Klaver DW, Wilce MC, Cui H, Hung AC, Gasperini R, Foa L, Small DH. Is BACE 1 a suitable therapeutic target for the treatment of Alzheimer’s disease? Current strategies and future directions. Biol Chem. 2010; 391 (8): 849-59.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E, Slutsky I. Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci. 2009; 12 (12): 1567-1576.</mixed-citation><mixed-citation xml:lang="en">Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E, Slutsky I. Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci. 2009; 12 (12): 1567-1576.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L Kirby L, Rovira MB, Forette F, Orgogozo JM. Clinical effects of Abeta immunization (AN 1792) in patients with AD in AN interrupted trial. Neurology. 2005;64 (9): 1553-1562.</mixed-citation><mixed-citation xml:lang="en">Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L Kirby L, Rovira MB, Forette F, Orgogozo JM. Clinical effects of Abeta immunization (AN 1792) in patients with AD in AN interrupted trial. Neurology. 2005;64 (9): 1553-1562.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Bayer AJ, Bullock R, Jones RW, Wilkinson D, Paterson KR, Jenkins L, Millais SB, Donoghue S. Evaluation of the safety and immunogenicity of synthetic Abeta42 (AN 1792) in patients with AD. Neurology. 2005; 64 (1): 94-101.</mixed-citation><mixed-citation xml:lang="en">Bayer AJ, Bullock R, Jones RW, Wilkinson D, Paterson KR, Jenkins L, Millais SB, Donoghue S. Evaluation of the safety and immunogenicity of synthetic Abeta42 (AN 1792) in patients with AD. Neurology. 2005; 64 (1): 94-101.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JA. Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet. 2008; 372 (9634): 216-23.</mixed-citation><mixed-citation xml:lang="en">Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JA. Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet. 2008; 372 (9634): 216-23.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Arai H, Suzuki H, Yoshiyama T: Vanutide cridificar and the QS-21 adjuvant in Japanese subjects with mild to moderate Alzheimer’s disease: Results from two phase 2 studies. Curr Alzheimer Res 2015; 12: 242-254.</mixed-citation><mixed-citation xml:lang="en">Arai H, Suzuki H, Yoshiyama T: Vanutide cridificar and the QS-21 adjuvant in Japanese subjects with mild to moderate Alzheimer’s disease: Results from two phase 2 studies. Curr Alzheimer Res 2015; 12: 242-254.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Pasquier F, Sadowsky C, Holstein A, Leterme Gle P, Peng Y, Jackson N, et al. Two phase 2 multiple ascending-dose studies of vanutide cridificar (ACC-001) and QS-21 adjuvant in mild-tomoderate Alzheimer’s disease. J Alzheimer Dis 2016; 51: 1131-1143.</mixed-citation><mixed-citation xml:lang="en">Pasquier F, Sadowsky C, Holstein A, Leterme Gle P, Peng Y, Jackson N, et al. Two phase 2 multiple ascending-dose studies of vanutide cridificar (ACC-001) and QS-21 adjuvant in mild-tomoderate Alzheimer’s disease. J Alzheimer Dis 2016; 51: 1131-1143.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">van Dyck CH, Sadowsky C, Le Prince Leterme G, Booth K, Peng Y, et al. Vanutide cridificar (ACC-001) and QS-21 adjuvant in individuals with early Alzheimer’s disease: Amyloid imaging positron emission tomography and safety results from a phase 2 study. J Prev Alzheimers Dis 2016; 3: 75-84.</mixed-citation><mixed-citation xml:lang="en">van Dyck CH, Sadowsky C, Le Prince Leterme G, Booth K, Peng Y, et al. Vanutide cridificar (ACC-001) and QS-21 adjuvant in individuals with early Alzheimer’s disease: Amyloid imaging positron emission tomography and safety results from a phase 2 study. J Prev Alzheimers Dis 2016; 3: 75-84.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Farlow MR, Andreasen N, Riviere ME, Vostiar I, Vitaliti A, Sovago J, et al. Long-term treatment with active Abeta immunotherapy with CAD 106 in mild Alzheimer’s disease. Alzheimers Res Ther 2015: 7: 23.</mixed-citation><mixed-citation xml:lang="en">Farlow MR, Andreasen N, Riviere ME, Vostiar I, Vitaliti A, Sovago J, et al. Long-term treatment with active Abeta immunotherapy with CAD 106 in mild Alzheimer’s disease. Alzheimers Res Ther 2015: 7: 23.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Winblad B, Andreasen N, Minthon L, Floesser A, Imbert G, Dumortier T, et al. Safety, tolerability, and antibody response of active Abeta immunotherapy with CAD 106 in patients with Alzheimer’s disease: Randomised, double-blind, placebo-controlled, first-inhuman study. Lancet Neurol (2012): 11: 597-604.</mixed-citation><mixed-citation xml:lang="en">Winblad B, Andreasen N, Minthon L, Floesser A, Imbert G, Dumortier T, et al. Safety, tolerability, and antibody response of active Abeta immunotherapy with CAD 106 in patients with Alzheimer’s disease: Randomised, double-blind, placebo-controlled, first-inhuman study. Lancet Neurol (2012): 11: 597-604.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Montoliu-Gaya L, Villegas S Abeta-Immunotherapeutic strategies: a wide range of approaches for Alzheimer’s disease treatment. Expert Rev Mol Med 2016; 18: e13.</mixed-citation><mixed-citation xml:lang="en">Montoliu-Gaya L, Villegas S Abeta-Immunotherapeutic strategies: a wide range of approaches for Alzheimer’s disease treatment. Expert Rev Mol Med 2016; 18: e13.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Sarazin M, Dorothee G, de Souza LC, Aucouturier P Immunotherapy in Alzheimer’s disease: Do we have all the pieces of the puzzle? Biol Psychiatry 2013; 74: 329-332.</mixed-citation><mixed-citation xml:lang="en">Sarazin M, Dorothee G, de Souza LC, Aucouturier P Immunotherapy in Alzheimer’s disease: Do we have all the pieces of the puzzle? Biol Psychiatry 2013; 74: 329-332.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Reiman EM, Langbaum JB, Fleisher AS, Caselli RJ, Chen K, Ayutyanont N, et al. Alzheimer’s Prevention Initiative: A plan to accelerate the evaluation of presymptomatic treatments. J Alzheimers Dis. 2011: 26 (suppl 3): 321-329.</mixed-citation><mixed-citation xml:lang="en">Reiman EM, Langbaum JB, Fleisher AS, Caselli RJ, Chen K, Ayutyanont N, et al. Alzheimer’s Prevention Initiative: A plan to accelerate the evaluation of presymptomatic treatments. J Alzheimers Dis. 2011: 26 (suppl 3): 321-329.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Laskowitz DT, Kolls BJ. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2010; 74 (24): 2026.</mixed-citation><mixed-citation xml:lang="en">Laskowitz DT, Kolls BJ. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2010; 74 (24): 2026.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, Sabbagh M, Honig LS, Doody R, van Dyck CH, Mulnard R, Barakos J, Gregg KM, Liu E, Lieberburg I, Schenk D, Black R, Grundman M. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009;73 (24): 2061-2070.</mixed-citation><mixed-citation xml:lang="en">Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, Sabbagh M, Honig LS, Doody R, van Dyck CH, Mulnard R, Barakos J, Gregg KM, Liu E, Lieberburg I, Schenk D, Black R, Grundman M. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009;73 (24): 2061-2070.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Cummings J, Cho W, Ward M, Friesenhahn M, Brunstein F, Honigberg L, et al. (2014): A randomized, double-blind, placebo-controlled phase 2 study to evaluate the efficacy and safety of crenezumab in patients with mild to moderate Alzheimer’s disease. Presented at Alzheimer’s Association International Conference (AAIC), Copenhagen, Denmark, July 16, 2014.</mixed-citation><mixed-citation xml:lang="en">Cummings J, Cho W, Ward M, Friesenhahn M, Brunstein F, Honigberg L, et al. (2014): A randomized, double-blind, placebo-controlled phase 2 study to evaluate the efficacy and safety of crenezumab in patients with mild to moderate Alzheimer’s disease. Presented at Alzheimer’s Association International Conference (AAIC), Copenhagen, Denmark, July 16, 2014.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Salloway S, Cho W, Clayton D, Honigberg L, Rabe C, Friesenhahn M, et al. (2014): Amyloid PET imaging results from a study to evaluate the impact of crenezumab on fibrillar amyloid in patients with mild-tomoderate Alzheimer’s disease. Presented at Clinical Trials on Alzheimer’s Disease (CTAD), Philadelphia, PA, November 20, 2014.</mixed-citation><mixed-citation xml:lang="en">Salloway S, Cho W, Clayton D, Honigberg L, Rabe C, Friesenhahn M, et al. (2014): Amyloid PET imaging results from a study to evaluate the impact of crenezumab on fibrillar amyloid in patients with mild-tomoderate Alzheimer’s disease. Presented at Clinical Trials on Alzheimer’s Disease (CTAD), Philadelphia, PA, November 20, 2014.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Honigberg L, Clayton D, Cho W, Rabe C, Friesenhahn M, Ward M, et al. (2014): Biomarker results from the crenezumab anti-Ab phase 2 biomarker trial. Presented at Clinical Trials on Alzheimer’s Disease (CTAD), Philadelphia, PA, November 20-22, 2014.</mixed-citation><mixed-citation xml:lang="en">Honigberg L, Clayton D, Cho W, Rabe C, Friesenhahn M, Ward M, et al. (2014): Biomarker results from the crenezumab anti-Ab phase 2 biomarker trial. Presented at Clinical Trials on Alzheimer’s Disease (CTAD), Philadelphia, PA, November 20-22, 2014.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. (2014): Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 370:311-321.</mixed-citation><mixed-citation xml:lang="en">Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. (2014): Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 370:311-321.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, et al. (2012): Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimers Dement 8: 261-271.</mixed-citation><mixed-citation xml:lang="en">Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, et al. (2012): Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimers Dement 8: 261-271.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Landen JW, Zhao Q, Cohen S, Borrie M, Woodward M, Billing CB Jr, Bales K, Alvey C, McCush F, Yang J, Kupiec JW, Bednar MM. Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: a phase I, randomized, placebo-controlled, double-blind, dose-escalation study. Clin Neuropharmacol. 2013; 36 (1): 14-23.</mixed-citation><mixed-citation xml:lang="en">Landen JW, Zhao Q, Cohen S, Borrie M, Woodward M, Billing CB Jr, Bales K, Alvey C, McCush F, Yang J, Kupiec JW, Bednar MM. Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: a phase I, randomized, placebo-controlled, double-blind, dose-escalation study. Clin Neuropharmacol. 2013; 36 (1): 14-23.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Burstein AH, Zhao Q, Ross J, Styren S, Landen JW, Ma WW, McCush F, Alvey C, Kupiec JW, Bednar MM. Safety and pharmacology of ponezumab (PF-04360365) after a single 10-minute intravenous infusion in subjects with mild to moderate Alzheimer disease. Clin Neuropharmacol. 2013; 36 (1): 8-13.</mixed-citation><mixed-citation xml:lang="en">Burstein AH, Zhao Q, Ross J, Styren S, Landen JW, Ma WW, McCush F, Alvey C, Kupiec JW, Bednar MM. Safety and pharmacology of ponezumab (PF-04360365) after a single 10-minute intravenous infusion in subjects with mild to moderate Alzheimer disease. Clin Neuropharmacol. 2013; 36 (1): 8-13.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">La Porte SL, Bollini SS, Lanz TA, Abdiche YN, Rusnak AS, Ho WH, Kobayashi D, Harrabi O, Pappas D, Mina EW, Milici AJ, Kawabe TT, Bales K, Lin JC, Pons J. Structural basis of C-terminal beta-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer's disease. J Mol Biol. 2012;421 (4-5): 525-536.</mixed-citation><mixed-citation xml:lang="en">La Porte SL, Bollini SS, Lanz TA, Abdiche YN, Rusnak AS, Ho WH, Kobayashi D, Harrabi O, Pappas D, Mina EW, Milici AJ, Kawabe TT, Bales K, Lin JC, Pons J. Structural basis of C-terminal beta-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer's disease. J Mol Biol. 2012;421 (4-5): 525-536.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, et al. (2012): Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol 69: 198-207.</mixed-citation><mixed-citation xml:lang="en">Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, et al. (2012): Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol 69: 198-207.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Lasser R, Ostrowitzki S, Scheltens P, Boada M, Dubois B, Dorflinger E, et al. (2015): Efficacy and safety of gantenerumab in prodromal Alzheimer’s disease: Results from scarlet road-a global, multicenter trial. Alzheimers Dement 11 (suppl): 331-332.</mixed-citation><mixed-citation xml:lang="en">Lasser R, Ostrowitzki S, Scheltens P, Boada M, Dubois B, Dorflinger E, et al. (2015): Efficacy and safety of gantenerumab in prodromal Alzheimer’s disease: Results from scarlet road-a global, multicenter trial. Alzheimers Dement 11 (suppl): 331-332.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, et al. (2016): Safety and tolerability of BAN2401 - a clinical study in Alzheimer’s disease with a protofibril selective Abeta antibody. Alzheimers Res Ther 8: 14.</mixed-citation><mixed-citation xml:lang="en">Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, et al. (2016): Safety and tolerability of BAN2401 - a clinical study in Alzheimer’s disease with a protofibril selective Abeta antibody. Alzheimers Res Ther 8: 14.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, MaierM, Dunstan R, Salloway S, Chen T, Ling Y, O'Gorman J, Qian F, Arastu M, LiM, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A. The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature. 2016; 537 (7618): 50-56.</mixed-citation><mixed-citation xml:lang="en">Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, MaierM, Dunstan R, Salloway S, Chen T, Ling Y, O'Gorman J, Qian F, Arastu M, LiM, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A. The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature. 2016; 537 (7618): 50-56.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Carlson C, Siemers E, Hake A, Case M, Hayduk R, Suhy J, Oh J, Barakos J. Amyloid-related imaging abnormalities from trials of solanezumab for Alzheimer's disease. Alzheimers Dement (Amst). 2016; 2: 75-85.</mixed-citation><mixed-citation xml:lang="en">Carlson C, Siemers E, Hake A, Case M, Hayduk R, Suhy J, Oh J, Barakos J. Amyloid-related imaging abnormalities from trials of solanezumab for Alzheimer's disease. Alzheimers Dement (Amst). 2016; 2: 75-85.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Salloway S, Sperling R, Keren R, Porsteinsson AP, van Dyck CH, Tariot PN, Gilman S, Arnold D, Abushakra S, Hernandez C, Crans G, Liang E, Quinn G, Bairu M, Pastrak A, Cedarbaum JM. A phase 2 randomized trial of ELND 005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology. 2011;77 (13): 1253-1262.</mixed-citation><mixed-citation xml:lang="en">Salloway S, Sperling R, Keren R, Porsteinsson AP, van Dyck CH, Tariot PN, Gilman S, Arnold D, Abushakra S, Hernandez C, Crans G, Liang E, Quinn G, Bairu M, Pastrak A, Cedarbaum JM. A phase 2 randomized trial of ELND 005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology. 2011;77 (13): 1253-1262.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Aisen PS, Gauthier S, Ferris SH, Saumier D, Haine D, Garceau D, Duong A, Suhy J, Oh J, Lau WC, Sampalis J. Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase study). Arch Med Sci. 2011;7 (1): 102-111.</mixed-citation><mixed-citation xml:lang="en">Aisen PS, Gauthier S, Ferris SH, Saumier D, Haine D, Garceau D, Duong A, Suhy J, Oh J, Lau WC, Sampalis J. Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase study). Arch Med Sci. 2011;7 (1): 102-111.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Greenberg SM, Rosand J, Schneider AT, Creed Pettigrew L Gandy SE, Rovner B, Fitzsimmons BF, Smith EE, Edip Gurol M, Schwab K, Laurin J, Garceau D. A phase 2 study of tramiprosate for cerebral amyloid angiopathy. Alzheimer Dis Assoc Disord. 2006;20 (4): 269-274.</mixed-citation><mixed-citation xml:lang="en">Greenberg SM, Rosand J, Schneider AT, Creed Pettigrew L Gandy SE, Rovner B, Fitzsimmons BF, Smith EE, Edip Gurol M, Schwab K, Laurin J, Garceau D. A phase 2 study of tramiprosate for cerebral amyloid angiopathy. Alzheimer Dis Assoc Disord. 2006;20 (4): 269-274.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Gervais F, Paquette J, Morissette C, Krzywkowski P, Yu M, Azzi M, Lacombe D, Kong X, Aman A, Laurin J, Szarek WA, Tremblay P. Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging. 2007; 28 (4): 537-547.</mixed-citation><mixed-citation xml:lang="en">Gervais F, Paquette J, Morissette C, Krzywkowski P, Yu M, Azzi M, Lacombe D, Kong X, Aman A, Laurin J, Szarek WA, Tremblay P. Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging. 2007; 28 (4): 537-547.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov. 2011; 10 (9): 698-712.</mixed-citation><mixed-citation xml:lang="en">Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov. 2011; 10 (9): 698-712.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Nie Q, Du XG, Geng MY. Small molecule inhibitors of amyloid beta peptide aggregation as a potential therapeutic strategy for Alzheimer's disease. Acta Pharmacol Sin. 2011; 32 (5): 545-551.</mixed-citation><mixed-citation xml:lang="en">Nie Q, Du XG, Geng MY. Small molecule inhibitors of amyloid beta peptide aggregation as a potential therapeutic strategy for Alzheimer's disease. Acta Pharmacol Sin. 2011; 32 (5): 545-551.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Karran E. Recent trial shows that solanezumab has disease modifying effects. BMJ. 2015; 351: h4528.</mixed-citation><mixed-citation xml:lang="en">Karran E. Recent trial shows that solanezumab has disease modifying effects. BMJ. 2015; 351: h4528.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Siemers ER, Sundell KL, Carlson C, Case M, Sethuraman G, Liu-Seifert H, Dowsett SA, Pontecorvo MJ, Dean RA, Demattos R. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer's disease patients. Alzheimers Dement. 2016; 12 (2): 110-120.</mixed-citation><mixed-citation xml:lang="en">Siemers ER, Sundell KL, Carlson C, Case M, Sethuraman G, Liu-Seifert H, Dowsett SA, Pontecorvo MJ, Dean RA, Demattos R. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer's disease patients. Alzheimers Dement. 2016; 12 (2): 110-120.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Barrera-Ocampo A, Lopera F. Amyloid-beta immunotherapy: the hope for Alzheimer disease? Colomb Med (Cali). 2016; 47 (4): 203-212.</mixed-citation><mixed-citation xml:lang="en">Barrera-Ocampo A, Lopera F. Amyloid-beta immunotherapy: the hope for Alzheimer disease? Colomb Med (Cali). 2016; 47 (4): 203-212.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Li L Sengupta A, Haque N, Grundkelqbal I, Iqbal K. Memantine inhibits and reverses the Alzheimer’s type abnormal hyperphosphorylation of tau and assotiated neurodegeneration. FEBS Letters. 2004; 566 (1-3): 261-269.</mixed-citation><mixed-citation xml:lang="en">Li L Sengupta A, Haque N, Grundkelqbal I, Iqbal K. Memantine inhibits and reverses the Alzheimer’s type abnormal hyperphosphorylation of tau and assotiated neurodegeneration. FEBS Letters. 2004; 566 (1-3): 261-269.</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. The Cochrane database of systematic reviews. 2006; 2: CD 003154</mixed-citation><mixed-citation xml:lang="en">McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. The Cochrane database of systematic reviews. 2006; 2: CD 003154</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984; 141 (11): 1356-1364.</mixed-citation><mixed-citation xml:lang="en">Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984; 141 (11): 1356-1364.</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Matsunaga S, Kishi T, Iwata N. Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis. PLoS One. 2015; 10 (4): e0123289.</mixed-citation><mixed-citation xml:lang="en">Matsunaga S, Kishi T, Iwata N. Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis. PLoS One. 2015; 10 (4): e0123289.</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ, et al. Memantine in moderate-to-severe Alzheimer's disease. The New England journal of medicine. 2003; 348 (14): 1333-1341.</mixed-citation><mixed-citation xml:lang="en">Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ, et al. Memantine in moderate-to-severe Alzheimer's disease. The New England journal of medicine. 2003; 348 (14): 1333-1341.</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Peskind ER, Potkin SG, Pomara N, Ott BR, Graham SM, Olin JT, et al. Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry. 2006; 14 (8): 704-715</mixed-citation><mixed-citation xml:lang="en">Peskind ER, Potkin SG, Pomara N, Ott BR, Graham SM, Olin JT, et al. Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry. 2006; 14 (8): 704-715</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Bakchine S, Loft H. Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. Journal of Alzheimer's disease: JAD. 2007; 11 (4): 471-479.</mixed-citation><mixed-citation xml:lang="en">Bakchine S, Loft H. Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. Journal of Alzheimer's disease: JAD. 2007; 11 (4): 471-479.</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">van Dyck CH, Tariot PN, Meyers B, Malca Resnick E, Memantine MEMMDSG. A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer disease and associated disorders. 2007; 21 (2): 136-143.</mixed-citation><mixed-citation xml:lang="en">van Dyck CH, Tariot PN, Meyers B, Malca Resnick E, Memantine MEMMDSG. A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer disease and associated disorders. 2007; 21 (2): 136-143.</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Schmidt R, Ropele S, Pendl B, Ofner P, Enzinger C, Schmidt H, et al. Longitudinal multimodal imaging in mild to moderate Alzheimer disease: a pilot study with memantine. Journal of neurology, neurosurgery, and psychiatry. 2008; 79 (12): 1312-1317.</mixed-citation><mixed-citation xml:lang="en">Schmidt R, Ropele S, Pendl B, Ofner P, Enzinger C, Schmidt H, et al. Longitudinal multimodal imaging in mild to moderate Alzheimer disease: a pilot study with memantine. Journal of neurology, neurosurgery, and psychiatry. 2008; 79 (12): 1312-1317.</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Kitamura S, Homma A, Nakamura Y. Late phase II study of mementine hydrochloride, a new NMDA receptor antagonist, in pa tients with moderate to severe Alzheimer's disease. Jpn J Geriatr Psychiat. 2011; 22 (4): 453-463.</mixed-citation><mixed-citation xml:lang="en">Kitamura S, Homma A, Nakamura Y. Late phase II study of mementine hydrochloride, a new NMDA receptor antagonist, in pa tients with moderate to severe Alzheimer's disease. Jpn J Geriatr Psychiat. 2011; 22 (4): 453-463.</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Nakamura Y, Homma A, Kitamura S, Yoshimura I. Phase IIIstudy of mementine hydrochloride, a new NMDA receptor antagonist, in patients with moderate to severe Alzheimer's disease. Jpn J Geriatr Psychiat. 2011; 22 (4): 464-І73.</mixed-citation><mixed-citation xml:lang="en">Nakamura Y, Homma A, Kitamura S, Yoshimura I. Phase IIIstudy of mementine hydrochloride, a new NMDA receptor antagonist, in patients with moderate to severe Alzheimer's disease. Jpn J Geriatr Psychiat. 2011; 22 (4): 464-І73.</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R, et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. The New England journal of medicine. 2012; 366 (10): 893-903.</mixed-citation><mixed-citation xml:lang="en">Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R, et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. The New England journal of medicine. 2012; 366 (10): 893-903.</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Wang T, Huang Q, Reiman EM, Chen K, Li X, Li G, et al. Effects of memantine on clinical ratings, fluorodeoxyglucose positron emission tomography measurements, and cerebrospinal fluid assays in patients with moderate to severe Alzheimer dementia: a 24-week, randomized, clinical trial. J Сііп Psychopharmacol. 2013; 33 (5): 636-642.</mixed-citation><mixed-citation xml:lang="en">Wang T, Huang Q, Reiman EM, Chen K, Li X, Li G, et al. Effects of memantine on clinical ratings, fluorodeoxyglucose positron emission tomography measurements, and cerebrospinal fluid assays in patients with moderate to severe Alzheimer dementia: a 24-week, randomized, clinical trial. J Сііп Psychopharmacol. 2013; 33 (5): 636-642.</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Li L, Sengupta A, Haque N, Grundke-Iqbal I, Iqbal K. Memantine inhibits and reverses the Alzheimer’s type abnormal hyperphosphorylation of tau and assotiated neurodegeneration. FEBS Letters. 2004; 566 (1-3): 261-269.</mixed-citation><mixed-citation xml:lang="en">Li L, Sengupta A, Haque N, Grundke-Iqbal I, Iqbal K. Memantine inhibits and reverses the Alzheimer’s type abnormal hyperphosphorylation of tau and assotiated neurodegeneration. FEBS Letters. 2004; 566 (1-3): 261-269.</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Куташов В. А., Самсонов А. С. Комплаентность и качество терапии болезни Альцгеймера при приеме меманталя. РМЖ. 2014; 22: 1603-1605.</mixed-citation><mixed-citation xml:lang="en">Куташов В. А., Самсонов А. С. Комплаентность и качество терапии болезни Альцгеймера при приеме меманталя. РМЖ. 2014; 22: 1603-1605.</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Ширяев О. Ю., Шаповалов Д. А., Полозова Т. М., Гончарова О. В., Кузнецова Н. А., Черенкова Е. В., Федорова Е. Ю. Сравнение эффективности и безопасности меманталя и оригинального препарата мемантин при легкой и умеренной деменции при болезни Альцгеймера. Журнал неврологии и психиатрии им. С. С. Корсакова. 2015; 115 (10): 56-61.</mixed-citation><mixed-citation xml:lang="en">Ширяев О. Ю., Шаповалов Д. А., Полозова Т. М., Гончарова О. В., Кузнецова Н. А., Черенкова Е. В., Федорова Е. Ю. Сравнение эффективности и безопасности меманталя и оригинального препарата мемантин при легкой и умеренной деменции при болезни Альцгеймера. Журнал неврологии и психиатрии им. С. С. Корсакова. 2015; 115 (10): 56-61.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
