Neurology, Neuropsychiatry, Psychosomatics

Advanced search

The development and treatment of Alzheimer’s disease: Some genetic aspects

Full Text:


The paper gives an update on the occurrence and development of Alzheimer’s disease (AD), a condition manifesting itself as a steady reduction in memory. AD is common in the modern population. The reason for its higher incidence rate is the specific features of the current information sphere. Genetic factors that both directly lead to the development of AD and indirectly influence its occurrence are also imperative. At the present time, the genetic bank of mutations associated with the development of AD contains information on more than 300 different mutations. Genetic predetermination of this disease has a negative impact on prognosis and prospects for patient treatment.

Patients and methods. The distribution of hereditary forms of AD in a Russian population was analyzed at the Clinic of Nervous System Diseases, I.M. Sechenov First Moscow State Medical University. The investigation enrolled 46 patients (13 men and 33 women) who met the international criteria for AD; all had its proven hereditary history. The patients' mean age was 73.7±8.3 years in the men and 73.4±8.5 in the women; the mean disease duration was 29.6±12.4 and 28.0±18.8 months, respectively. The incidence of AD was estimated depending on age, comorbidity, degree of cognitive impairments, and pattern of the disease. Its history was rated using a questionnaire. No genome mapping was carried out.

Results and discussion. The patients were divided into two groups: 1) presenile AD (age at its onset less than 65 years; n=8) and 2) senile AD (age at its onset more than 65 years; n=38). There was a preponderance of patients with mild dementia in both groups; however, in the patients with senile AD, the latter was diagnosed at the stage of moderate cognitive impairments in 7.9% of cases. Comorbidity was mild in all the patients. Depression and behavioral disorders were noted in half of the patients with AD; at the same time, behavioral and emotional disorders were significantly more common in the presenile and senile AD groups, respectively. The prevalence of senile AD was shown to be 4.7 times
greater than that of presenile AD, as shown by our data). The performed investigation could reveal some features of the course and clinical presentation of both genetically determined AD as a whole and its senile and presenile forms in particular.

About the Authors

I. S. Preobrazhenskaya
I.M. Sechenov First Moscow State Medical University, Moscow, Russia 8, Trubetskaya St., Build. 2, Moscow 119991
Russian Federation

N. S. Snitskaya
I.M. Sechenov First Moscow State Medical University, Moscow, Russia 8, Trubetskaya St., Build. 2, Moscow 119991
Russian Federation


1. Аршавский ЮИ. Роль аутоиммуных механизмов в инициации болезни Альцгеймера. Иммунология. 2011;32(4):216–21. [Arshavskii YuI. The role of autoimmune mechanisms in the initiation of Alzheimer disease. Immunologiya. 2011;32(4):216–21. (In Russ.)]

2. Преображенская ИС. Десятый международный конгресс «Болезни Альцгеймера и Паркинсона: достижения, концепции и новые вызовы» (Барселона, Испания, 09.03.2011–13.03.2011). Неврологический журнал. 2011;16(4):60–4. [Preobrazhenskaya IS. The 10th international congress «Alzheimer’s and Parkinson’s Diseases: Advances, Concepts and New Challenges» (Barcelona, Spain, 09.03.2011–13.03.2011). Nevrologicheskii zhurnal. 2011;16(4):60–4. (In Russ.)]

3. Гаврилова СИ. Болезнь Альцгеймера: современные подходы к диагностике и лечению. Клиническая фармакология и терапия. 2002;11(4):1–8. [Gavrilova SI. Alzheimer’s disease: modern approaches to diagnostics and treatment. Klinicheskaya farmakologiya i terapiya. 2002;11(4):1–8. (In Russ.)]

4. Bird TD. Genetic aspects of Alzheimer disease. Genet Med. 2008 Apr;10(4):231–9. DOI: 10.1097/GIM.0b013e31816b64dc.

5. Farrer LA, Bowirrat A, Friedland RP, et al. Identification of multiple loci for Alzheimer disease in a consanguineous Israeli–Arab community. Hum Mol Genet. 2003;12(4):415–22. DOI:

6. Суханов АВ, Короленко ЦП, Виноградова ТЕ и др. Молекулярно-генетические факторы риска болезни Альцгеймера. Журнал неврологии и психиатрии им. С.С. Корсакова. 2001;101(1):65–8. [Sukhanov AV, Korolenko TsP, Vinogradova TE, et al. Molecular and genetic risk factors of Alzheimer’s disease. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2001;101(1):65–8. (In Russ.)]

7. Iqbal K, Winblad B, Nishumura T, et al. Alzheimer’s disease: biology, diagnosis and therapeutics. Chichester: J Willey and Sons Ltd; 1997. 831 р.

8. Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001;81(2):741–66.

9. Goate A, Chartier-Harlin MC, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature. 1991;349(6311):704–6. DOI:

10. Hardy J. Towards Alzheimer’s therapy based on genetic knowledge. Аnnu Rev Med. 2004;55:15–25. DOI: 1146/

11. Li Y, Grupe A. Genetics of late-onset Alzheimer’s disease: progress and prospect. Pharmacogenomics. 2007 Dec;8(12):1747–55. DOI: 8.12.1747.

12. Соколик ВВ. Биохимия В-амилоидного пептида и болезнь Альцгеймера. Вопросы биологической, медицинской и фармацевтической химии. 2010;(3):3–8. [Sokolik VV. Biochemitry of β-amyloid protein and Alzheimer’s disease (a review). Voprosy biologicheskoi, meditsinskoi i farmatsevticheskoi khimii. 2010;(3):3–8. (In Russ.)]

13. Lott IT, Head E. Down syndrome and Alzheimer’s disease: a link between development and aging. Ment Retard Dev Disabil Res Rev. 2001;7(3):172–8. DOI: 10.1002/mrdd.1025.

14. Cardenas AM, Ardiles AO, Barraza N, et al. Role of tau protein in neuronal damage in Alzheimer’s disease and down syndrome. Arch Med Res. 2012;43(8):645–54. DOI: 10.1016/j.arcmed.2012.10.012. Epub 2012 Nov 7.

15. Haass C. Take five – BACE and the gamma-secretase quartet conduct Alzheimer’s amyloid beta-peptide generation. EMBO J. 2004;23(3):483–8. DOI:

16. Успенская ОА, Захаров ВВ. Патогенетические и нейрохимические основы развития болезни Альцгеймера. Врач. 2010;(4):72–4. [Uspenskaya OA, Zakharov VV. Alzheimer's disease: pathogenetic and neurochemical bases of its development. Vrach. 2010;(4):72–4. (In Russ.)]

17. Su B, Wang X, Zheng L, et al. Abnormal mitochondrial dynamics and neurodegenerative diseases. Biochim Biophys Acta. 2010 Jan;1802(1):135–42. DOI: Epub 2009 Sep 30.

18. Smith MA, Zhu X, Tabaton M, et al. Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. J Alzheimers Dis. 2010 Jan;19(1):363–72.

19. Carvalho C, Correia SC, Santos RX, et al. Role of mitochondrial-mediated signaling pathways in Alzheimer disease and hypoxia. J Bioenerg Biomembr. 2009; 41(5):433–40. DOI: 10.1007/s10863-009-9247-1.

20. Opazo C, Huang X, Cherny RA, et al. Metalloenzyme-like activity of Alzheimer’s disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H(2)O(2). J Biol Chem. 2002 Oct 25;277(43):40302–8. DOI: Epub 2002 Aug 20.

21. Макдональд П. Генетическая диета ApoE. Решение проблем веса, повышенного холестерина, сердечно-сосудистых заболеваний. Серия: Медицина намерения. Cанкт-Петербург: Издательство «Весь»; 2011. 560 с. [Makdonal'd P. Geneticheskaya dieta ApoE. Reshenie problem vesa, povyshennogo kholesterina, serdechno-sosudistykh zabolevanii. Seriya: Meditsina namereniya [Genetic diet of ApoE. The solution of problems of the weight, the raised cholesterol, cardiovascular diseases]. St-Petersburg: Izdatel'stvo «Ves'»; 2011. 560 p.]

22. Sensi SL, Paoletti P, Bush AI, Sekler I. Zinc in the physiology and pathology of the CNS. Nat Rev Neurosci. 2009 Nov;10(11):780–91. DOI: Epub 2009 Oct 14.

23. Xie L, Hongyi K, Qiwu X, et al. Sleep drives metabolite clearanse from the adult brain. Science. 2013;342(6156):342–73.

24. Parsons CG, Danysz W, Quack G. Glutamate in CNS disorders as a target for drug development: an update. Drug News Perspect. 1998;11(9):523–69. DOI: 1358/dnp.1998.11.9.863689.

25. Яхно НН, Захаров ВВ, Локшина АБ и др. Деменции: Руководство для врачей. 3-е изд. Москва: МЕДпреcс-информ; 2011. 272 с. [Yakhno NN, Zakharov VV, Lokshina AB, et al. Dementsii: Rukovodstvo dlya vrachei [Dementias: the management for doctors]. 3nd ed. Moscow: MEDpress-inform; 2011. 272 p.]

26. Thinakaran G. The role of presenilins in Alzheimer’s disease. J Clin Invest. 1999;104(10):1321–7. DOI:

27. Ashford JW. APOE genotype effects on Alzheimer’s disease onset and epidemiology. J Mol Neurosci. 2004;23(3):157–65. DOI:

28. Papassotiropoulos A, Fountoulakis M, Dunckley T, et al. Genetics, transcriptomics, and proteomics of Alzheimer’s disease. J Clin Psychiatry. 2006 Apr;67(4):652–70. DOI:

29. Alonso Vilatela ME, Lopez-Lopez M, Yescas Gomez P. Genetics of Alzheimer’s disease. Arch Med Res. 2012;43(8):622–31. DOI: 10.1016/j.arcmed.2012.10.017.

30. Wahlster L, Arimon M, Nasser-Ghodsi N, et al. Presenilin-1 adopts pathogenic conformation in normal aging and in sporadic Alzheimer’s disease. Acta Neuropathol. 2013 Feb;125(2):187–99. DOI: 10.1007/s00401-012-1065-6. Epub 2012 Nov 9

31. Oh SY, Ellenstein A, Chen CD, et al. Amyloid precursor protein interacts with notch receptors. J Neurosci Res. 2005;82(1):32–42.

32. Hoe HS, Tran TS, Matsuoka Y, et al. DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing. J Biol Chem. 2006;281(46):35176–85. DOI: Epub 2006 Sep 1.

33. Гаврилова СИ, Жариков ГА, Селезнева НВ. АпоЕ генотип и терапевтический ответ при болезни Альцгеймера. Врач. 2006;(5):8–13. [Gavrilova SI, Zharikov GA, Selezneva NV. Apoye a genotype and the therapeutic answer at Alzheimer’s disease. Vrach. 2006;(5):8–13. (In Russ.)]

34. Гаврилова СИ. Фармакотерапия болезни Альцгеймера. Москва: Пульс; 2003. 320 с. [Gavrilova SI. Farmakoterapiya bolezni Al'tsgeimera [Alzheimer’s disease pharmacotherapy]. Moscow: Pul's; 2003. 320 p.]

35. Lott IT, Head E. Alzheimer disease and Down syndrome: factors in pathogenesis. Neurobiol Aging. 2005 Mar;26(3):383–9. DOI: 2004.08.005.

36. Cacabelos R. Pharmacogenetic basis for therapeutic optimization in Alzheimer’s disease. Mol Diagn Ther. 2007;11(6):385–405. DOI:

37. Chace C, Pang D, Weng C, et al. Variants in CYP17 and CYP19 cytochrome P450 genes are associated with onset of Alzheimer's disease in women with Down syndrome. Journal of Alzheimer's Disease. 2012;28(3):601–12. DOI: 10.3233/JAD-2011-110860.

38. Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising of the NINCDSADRDRA criteria. Lancet Neurol. 2007;6(8):734–46. DOI:


For citations:

Preobrazhenskaya I.S., Snitskaya N.S. The development and treatment of Alzheimer’s disease: Some genetic aspects. Neurology, Neuropsychiatry, Psychosomatics. 2014;6(4):51-58. (In Russ.)

Views: 1667

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)