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Biochemistry (Moscow)

, Volume 82, Issue 2, pp 122–139 | Cite as

Biological basis for amyloidogenesis in Alzheimer’S disease

  • T. V. Andreeva
  • W. J. Lukiw
  • E. I. Rogaev
Review

Abstract

Certain cellular proteins normally soluble in the living organism under certain conditions form aggregates with a specific cross-β sheet structure called amyloid. These intraor 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.

Keywords

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

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Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • T. V. Andreeva
    • 1
    • 2
  • W. J. Lukiw
    • 3
    • 4
    • 5
  • E. I. Rogaev
    • 1
    • 2
    • 6
    • 7
  1. 1.Vavilov Institute of General GeneticsRussian Academy of SciencesMoscowRussia
  2. 2.Center for Brain Neurobiology and Neurogenetics, Institute of Cytology and GeneticsSiberian Branch of the Russian Academy of SciencesNovosibirskRussia
  3. 3.Louisiana State University Health Science CenterLSU Neuroscience CenterNew OrleansUSA
  4. 4.Department of OphthalmologyLouisiana State University Health Science CenterNew OrleansUSA
  5. 5.Department of NeurologyLouisiana State University Health Science CenterNew OrleansUSA
  6. 6.Department of PsychiatryUniversity of Massachusetts Medical School, Brudnick Neuropsychiatric Research InstituteWorcesterUSA
  7. 7.Lomonosov Moscow State UniversitySchool of Bioengineering and BioinformaticsMoscowRussia

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