Features of in vitro, in silico and transgenic models of Alzheimer’s disease

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The review examines the current in vitro, in silico and trangenic experimental models of Alzheimer’s disease, is widely used for comprehensive studies of the pathogenesis of chronic neurodegenerative process. The experimental model should have a constructive, face and predictive validity, i.e. it must be established based on the known mechanisms of the pathogenesis of the disease and to ensure the development of symptoms characteristic of the disease, the severity of the past shall be reduced by the action of pharmacological agents already tested. Noted that transgenic models have high face and proven constructive validity.

About the authors

V. V. Kolobov

Research Center of Neurology, Russian Academy of Medical Sciences

Email: f.neurochemistry@gmail.com
Russian Federation, Moscow

Z. I. Storozheva

Serbsky National Research Centre for Social and Forensic Psychiatry

Author for correspondence.
Email: f.neurochemistry@gmail.com
Russian Federation, Moscow


  1. Григоренко А.П., Рогаев Е.И. Молекулярные основы болезни Альцгеймера. Молекуляр. биология. 2007. 41 (2): 331–345.
  2. Колобов В.В., Давыдова Т.В., Захарова И.А. и др. Репрессирующее влияние антител к глутамату на экспрессию гена Dffb в мозге крыс при экспериментальной болезни Альцгеймера. Молекуляр. биология. 2012; 46 (5): 757–765.
  3. Костанян И.А., Жохов С.С., Сторожева З.И. и др. Нейропротекторное действие гексапептида HLDF-6 на нейроны гиппокампа крыс на модели болезни Альцгеймера in vivo и in vitro. Биоорган. химия. 2006; 32 (4): 399–407.
  4. Саранцева С.В., Шварцман А.Л. Болезнь Альцгеймера – амилоидоз или дисфункция синапсов? Уроки моделирования на Drosophila melanogaster. Экол. генетика. 2005; 3 (4): 19–25.
  5. Рогаев Е.И. Генетическая природа болезни Альцгеймера и других деменций и перспективы молекулярной диагностики. Вестник РАМН. 1999; 1: 33–39.
  6. Шварцман А.Л., Саранцева С.В., Рунова О.Л. и др. Мутации в гене пресенелина 1, наблюдаемые при семейных формах болезни Альцгеймера, подавляют межклеточные взаимодействия в трансфецированных фибробластах. Биофизика. 2010; 55 (5): 862–867.
  7. Шерстнёв В.В., Голубева О.Н., Грудень М.А. и др. Нейрогенез и нейроапоптоз в различных отделах зрелого мозга крыс Wistar. Нейрохимия. 2012; 29 (3): 206–212.
  8. Яхно Н.Н., Захаров В.В., Локшина А.Б. и др. Деменции: руководство для врачей. М.: МЕДпресс-информ, 2010: 272.
  9. Aggleton J.P. Understanding retrosplenial amnesia: insights from animal studies. Neuropsychologia. 2010; 48 (8): 2328–2338.
  10. Anastasio T.J. Data-driven modeling of Alzheimer disease pathogenesis. J. Theor. Biol. 2011; 290: 60–72.
  11. Autiero I., Saviano M., Langella E. In silico investigation and targeting of amyloid β oligomers of different size. Mol. Biosyst. 2013; 9(8): 2118–2124.
  12. Becker E.B., Bonni A. Beyond proliferation-cell cycle control of neuronal survival and differentiation in the developing mammalian brain. Semin. Cell. Dev. Biol. 2005; 16 (3): 439–448.
  13. Beier M. Alzheimer’s disease: epidemiology and risk factors. Adv. Stud. Pharm. 2005; 2 (4): 116–125.
  14. Bossy-Wetzel E., Schwarzenbacher R., Lipton S.A. Molecular pathways to neurodegeneration. Nat. Med. 2004; 10 (Suppl.): S2–S9.
  15. Bugos O., Bhide M., Zilka N. Beyond the rat models of human neurodegenerative disorders. Cell. Mol. Neurobiol. 2009; 29 (6–7):859–869.
  16. Cressoni J.C., Viswanathan G.M., Ferreira A.S., da Silva M.A. Alzheimer random walk model: two previously overlooked diffusion regimes. Phys. Rev. E. Stat. Nonlin. Soft. Matter Phys. 2012; 86 (4, Pt 1): 042101.
  17. Easton A., Sankaranarayanan S., Tanghe A. et al. Effects of subchronic donepezil on brain Abeta and cognition in a mouse model of Alzheimer’s disease. Psychopharmacology (Berl.). 2013; 230 (2):279–289.
  18. Farooque A.A. Neurodegeneration in neuronal trauma, neurodegenerative diseases, and neuropsychiatric disorders. Neurochemical aspects of neurotraumatic and neurodegenerative diseases. Ed.Farooque A.A. New York: Springer, 2010a: 1–25.
  19. Farooque A.A. Neurochemical aspects of neurodegenerative disease. Neurochemical aspects of neurotraumatic and neurodegenerative diseases. Ed. Farooque A.A. New York: Springer, 2010b: 249–324.
  20. Ferretti M.T., Partridge V., Leon W.C. et al. Transgenic mice as a model of pre-clinical Alzheimer’s disease. Curr. Alzheimer. Res. 2011;8 (1): 4–23.
  21. Fluhrer R., Haass Ch. Intramembrane proteolysis by γ-secretase and signal peptide peptidases. Intracellular traffic and neurodegenerative disorders. Eds. George-Hyslop P.H.St., Mobley W.C., Christen Y. Berlin: Springer, 2009: 11–26.
  22. Geerts H., Roberts P., Spiros A., Carr R. A strategy for developing new treatment paradigms for neuropsychiatric and neurocognitive symptoms in Alzheimer’s disease. Front Pharmacol. 2013; 4:44, doi: 10.3389/fphar.2013.00047.
  23. Ghorayeb I., Page G., Gaillard A., Jaber M. Animal models of neurodegenerative diseases. Neurochemical mechanisms in disease. Ed. Blass J.P. New York: Springer Science+Business Media, 2011: 49–101.
  24. Graeber M.B., Moran L.B. Mechanisms of cell death in neurodegenerative disease: fashion, fiction, and facts. Brain Pathol. 2002; 12 (3): 385–390.
  25. Greene J.D., Hodges J.R. Identification of famous faces and famous names in early Alzheimer’s disease. Relationship to anterograde episodic and general semantic memory. Brain. 1996; 119 (Pt 1): 111–128.
  26. Grothe M., Heisensen H., Teipel S.J. Atrophy of the cholinergic basal forebrain over the adult age range and in early stages of Alzheimer’s disease. Biol. Psychiatry. 2012; 71 (9): 805–813.
  27. Hardy J., Selkoe D.J. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. An updated summary of the amyloid hypothesis. Science. 2002; 297 (5580): 353–356.
  28. Hargus G., Ehrlich M., Hallmann A.-L., Kuhlmann T. Human stem cell models of neurodegeneration: a novel approach to study mechanisms of disease development. Acta Neuropathol. 2013; Dec 5: Epub ahead of print.
  29. He Y., Chen Z., Gong G., Evans A. Neuronal networks in Alzheimer’s disease. Neuroscientist. 2009; 15 (4): 333–350.
  30. Hutton M., Tolnay M., Jucker M. Induction of tau pathology by intracerebral infusion of amyloid beta-containing brain extract and by amyloid-beta deposition in APP x Tau transgenic mice. Am. J. Pathol. 2007; 171: 2012–2020.
  31. Jin S.C., Pastor P., Cooper B. et al. Pooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early-onset and familial Alzheimer’s disease Ibero-Americo cohort. Alzheimer’s Research & Therapy. 2012; 4: doi: 10.1186/alzrt137.
  32. Krantic S., Mechawar N., Reix S., Quirion R. Molecular basis of programmed cell death involved in neurodegeneration. Trends Neurosci. 2005; 28 (12): 670–676.
  33. Mandelkow E.-M., Thies E., Konzack S., Mandelkow E. Tau and intracellular transport in neurons. Intracellular traffic and neurodegenerative disorders. Eds. George-Hyslop P.H.St., Mobley W.C., Christen Y. Berlin: Springer, 2009: 59–70.
  34. McGeer P.L., McGeer E.G. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res. Rev. 1995; 21 (2): 195–218.
  35. McGeer P.L., Rogers J., McGeer E.G. Inflammation, anti-inflammatory agents and Alzheimer disease: the last 12 years. J. Alzheimers Dis. 2006; 9 (3, Suppl.): 271–276.
  36. Meeter M., Eijsackers E.V., Mulder J.L. Retrograde amnesia for autobiographical memories and public events in mild and moderate Alzheimer’s disease. J. Clin. Exp. Neuropsychol. 2006; 28 (6): 914–927.
  37. Mrak R.E. Neuropathology and the neuroinflammation idea. J. Alzheimer’s Dis. 2009; 18 (3): 473–481.
  38. Nguyen M.D., Mushynski W.E., Julien J.P. Cycling at the interface between neurodevelopment and neurodegeneration. Cell. Death. Differ. 2002; 9 (12): 1294–1306.
  39. Nielsen H.M., Ek D., Avdic U. et al. NG2 cells, a new trial for Alzheimer’s disease mechanisms? Acta Neuropahol. Commun. 2013; 1 (1): 7, doi: 10.1186/2051-5960-1-7.
  40. Piaceri I., Nacmias B., Sorbi S. Genetics of familial and sporadic Alzheimer’s disease. Front. Biosci. (Elite Ed.). 2013; 5: 167–177.
  41. Popova J., Ambroz P., Bar M. et al. Epidemiology of and risk factors for Alzheimer’s disease: a review. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech. Repub. 2012; 156 (2): 108–114.
  42. Rao A.V., Balachandran B. Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutr. Neurosci. 2002; 5 (5): 291–309.
  43. Reiter L.T., Potocki L., Chien S. et al. A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res. 2001; 11 (6): 1114–1125.
  44. Ross C.A., Poirier M.A. Protein aggregation and neurodegenerative disease. Nat. Med. 2004; 10 (Suppl.): S10–S17.
  45. Saura C.A., Choi S.-Y., Beglopoulos V. et al. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron. 2004; 42 (1): 23–36.
  46. Scholtzova H., Wadghiri Y.Z., Douadi M. et al. Memantine leads to behavioral improvement and amyloid reduction in Alzheimer’s-disease-model transgenic mice shown as by micromagnetic resonance imaging. J. Neurosci. Res. 2008; 86 (12): 2784–2791.
  47. Sikström S. Computational perspectives on neuromodulation of aging. Acta Neurochir. Suppl. 2007; 97 (Pt. 2): 513–518.
  48. Small G.W., Rabins P.V., Barry P.P. et al. Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s Association, and the American Geriatrics Society. JAMA. 1997; 278 (16): 1363–1371.
  49. Soto C. Unfolding the role of protein misfolding in neurodegenerative diseases. Nat. Rev. 2003; 4 (1): 49–60.
  50. Summers W.K. Clinical relevance: cytokines in Alzheimer’s disease. Cytokines and the brain. Eds Phelps C., Korneva E. Amsterdam: Elsevier, 2008: 507–526.
  51. Terry R.D., Peck A., DeTeresa R. et al. Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann. Neurol. 1981; 10 (2): 184–192.
  52. Vazin T., Ball. K.A., Lu H. et al. Efficient derivation of cortical glutamatergic neurons from human pluripotent stem cells: A model system to study neurotoxicity in Alzheimer’s disease. Neurobiol. Dis. 2013;62C: 62–72.
  53. Verdile G., Martins R.N. Molecular genetics of Alzheimer’s disease. Molecular biology of neuropsychiatric disorders. Ed. Wildenauer D.B. – Berlin, Heidelberg: Springer-Verlag, 2009: 229–276.
  54. Wadman M. US government sets out Alzheimer’s plan. Nature. 2012; 485 (7399): 426–427.
  55. Woodruff-Pak D.S. Animal models of Alzheimer’s disease: therapeutic implications. J. Alzheimer’s Dis. 2008; 15 (4): 507–521.

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Copyright (c) 2014 Kolobov V.V., Storozheva Z.I.

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