The Cellular Phase of Alzheimer's Disease

Cell. 2016 Feb 11;164(4):603-15. doi: 10.1016/j.cell.2015.12.056.


The amyloid hypothesis for Alzheimer's disease (AD) posits a neuron-centric, linear cascade initiated by Aβ and leading to dementia. This direct causality is incompatible with clinical observations. We review evidence supporting a long, complex cellular phase consisting of feedback and feedforward responses of astrocytes, microglia, and vasculature. The field must incorporate this holistic view and take advantage of advances in single-cell approaches to resolve the critical junctures at which perturbations initially amenable to compensatory feedback transform into irreversible, progressive neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Brain / pathology
  • Humans
  • Mice
  • Microglia / metabolism
  • Microglia / pathology
  • Neural Pathways
  • Oligodendroglia / pathology
  • Single-Cell Analysis


  • Amyloid beta-Peptides