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Untangling the role of tau in Alzheimer’s disease: A unifying hypothesis

  • Review Article
  • Published:
Translational Neuroscience

Abstract

Recent investigations into the etiology and pathogenesis of Alzheimer’s disease (AD) in the past few years have expanded to include previously unexplored and/or disconnected aspects of AD and related conditions at both the cellular and systemic levels of organization. These include how AD-associated abnormalities affect the cell cycle and neuronal differentiation state and how they recruit signal transduction, membrane trafficking and protein transcytosis mechanisms to produce a neurotoxic syndrome capable of spreading itself throughout the brain. The recent expansion of AD research into intercellular and new aspects of cellular degenerative mechanisms is causing a systemic re-evaluation of AD pathogenesis, including the roles played by well-studied elements, such as the generation of Aβ and tau protein aggregates. It is also changing our view of neurodegenerative diseases as a whole. Here we propose a conceptual framework to account for some of the emerging aspects of the role of tau in AD pathogenesis.

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Abbreviations

AD:

Alzheimer’s disease

FAD:

familial Alzheimer’s disease

LOAD:

late-onset Alzheimer’s disease

APP:

amyloid precursor protein

NFT:

neurofibrillary tangle

PHF:

paired helical filaments

Aβ:

beta-amyloid peptide

CTE:

chronic traumatic encephalopathy

CNS:

central nervous system

CSF:

cerebrospinal fluid

ROS:

reactive oxygen species

MT:

microtubule

ECF:

extracellular fluid

MTBR:

microtubule binding repeat

MAP:

microtubule associated protein

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  1. Department of Biological Sciences, University of Massachusetts Lowell, 198 Riverside Street, Lowell, MA, 01854, USA

    Neha Bhatia & Garth F. Hall

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  1. Neha Bhatia
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Bhatia, N., Hall, G.F. Untangling the role of tau in Alzheimer’s disease: A unifying hypothesis. Translat.Neurosci. 4, 115–133 (2013). https://doi.org/10.2478/s13380-013-0114-5

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