The role of Aβ and tau oligomers in the pathogenesis of Alzheimer's disease

Kiran Bhaskar, Bruce T. Lamb

Research output: Chapter in Book/Report/Conference proceedingChapter

6 Scopus citations

Abstract

Dense extracellular aggregates of amyloid β-protein (Aβ) in senile plaques (SPs) and intracellular aggregates of the hyperphosphorylated, microtubule-associated protein tau (MAPT) in neurofibrillary tangles (NFTs) within the brain are the key diagnostic hallmarks of Alzheimer's disease (AD). While initial studies focused on SPs and NFTs as the key pathogenic proteinaceous species that could account for the clinical features of AD, increasing evidence suggests that the fibrils of Aβ and MAPT are unlikely to be the unique neurotoxic entities responsible for AD pathogenesis. Instead, more recent studies have implicated small, soluble oligomeric species of both Aβ and MAPT. Indeed, a wide variety of Aβ and tau -oligomers have been described in both in vitro and in vivo systems that possess a diverse set of biological properties, including substantial synapto- and neurotoxicity. While many of these oligomers have been extensively characterized by novel biophysical, -biochemical, and immunological techniques, attributing particular functions and dysfunctions to particular oligomer structures in vivo has proven enormously difficult, as the different proteinaceous species are present in equilibrium and likely are contained within unique intracellular and extracellular environments. Nevertheless, a number of therapeutic strategies have been developed that seek to target Aβ and tau oligomerization for AD.

Original languageEnglish (US)
Title of host publicationNon-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases
PublisherSpringer Netherlands
Pages135-188
Number of pages54
Volume9789400727748
ISBN (Electronic)9789400727748
ISBN (Print)9400727739, 9789400727731
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Aβ oligomers
  • Neurofibrillary tangles
  • Neuropathology
  • Tau oligomers

ASJC Scopus subject areas

  • Medicine(all)

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