REVIEW: Biological Basis for Amyloidogenesis in Alzheimer’s Disease

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T. V. Andreeva^1,2*, W. J. Lukiw^3,4,5*, and E. I. Rogaev^1,2,6,7*

¹Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia; E-mail: andreeva@rogaevlab.ru, Evgeny.Rogaev@umassmed.edu

²Center for Brain Neurobiology and Neurogenetics, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

³Louisiana State University Health Science Center, LSU Neuroscience Center, 70112 New Orleans LA, USA

⁴Louisiana State University Health Science Center, Department of Ophthalmology, 70112 New Orleans LA, USA; E-mail: wlukiw@lsuhsc.edu

⁵Louisiana State University Health Science Center, Department of Neurology, 70112 New Orleans LA, USA

⁶University of Massachusetts Medical School, Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, 01604 Worcester, Massachusetts, USA

⁷Lomonosov Moscow State University, School of Bioengineering and Bioinformatics, 119234 Moscow, Russia

^* To whom correspondence should be addressed.

Received August 20, 2016; Revision received September 20, 2016

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Certain cellular proteins normally soluble in the living organism under certain conditions form aggregates with a specific cross-β sheet structure called amyloid. These intra- or extracellular insoluble aggregates (fibers or plaques) are hallmarks of many neurodegenerative pathologies including Alzheimer’s disease (AD), Huntington’s disease, Parkinson’s disease, prion disease, and other progressive neurological diseases that develop in the aging human central nervous system. Amyloid diseases (amyloidoses) are widespread in the elderly human population, a rapidly expanding demographic in many global populations. Increasing age is the most significant risk factor for neurodegenerative diseases associated with amyloid plaques. To date, nearly three dozen different misfolded proteins targeting brain and other organs have been identified in amyloid diseases and AD, the most prevalent neurodegenerative amyloid disease affecting over 15 million people worldwide. Here we (i) highlight the latest data on mechanisms of amyloid formation and further discuss a hypothesis on the amyloid cascade as a primary mechanism of AD pathogenesis and (ii) review the evolutionary aspects of amyloidosis, which allow new insight on human-specific mechanisms of dementia development.

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KEY WORDS: amyloidogenesis, amyloidosis, beta amyloid cleavage enzyme (BACE), β-amyloid precursor protein (APP), Alzheimer’s disease (AD), presenilins

DOI: 10.1134/S0006297917020043

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