title: The Cellular Phase of Alzheimer's Disease.
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.
authors.affiliation: 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.
authors.forename: Bart
authors.initials: B
authors.lastname: De Strooper
authors.affiliation: 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.
authors.forename: Eric
authors.initials: E
authors.lastname: Karran
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology; D006801:Humans; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009434:Neural Pathways; D009836:Oligodendroglia / Q000473:pathology; D059010:Single-Cell Analysis
chemical_list: D016229:Amyloid beta-Peptides