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

The Cellular Phase of Alzheimer's Disease.

Author information

1
VIB Center for the Biology of Disease, VIB-Leuven, 3000 Leuven, Belgium; Center for Human Genetics, Universitaire Ziekenhuizen and LIND, KU Leuven, 3000 Leuven, Belgium; Institute of Neurology, University College London, Queen Square, WC1N 3BG London, UK. Electronic address: bart.destrooper@cme.vib-kuleuven.be.
2
Center for Human Genetics, Universitaire Ziekenhuizen and LIND, KU Leuven, 3000 Leuven, Belgium; Institute of Neurology, University College London, Queen Square, WC1N 3BG London, UK; Alzheimer Research UK, Cambridge, CB21 6AD, UK.

Abstract

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.

PMID:
26871627
DOI:
10.1016/j.cell.2015.12.056
[Indexed for MEDLINE]
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