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Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability.

Abstract：

:Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ, which plays a central role in AD pathogenesis, is generated throughout the brain, yet some regions outside of the limbic and cerebral cortices are relatively spared from Aβ plaque deposition and synapse loss. Here, we examine neurons derived from iPSCs of patients harboring an amyloid precursor protein mutation to quantify AD-relevant phenotypes following directed differentiation to rostral fates of the brain (vulnerable) and caudal fates (relatively spared) in AD. We find that both the generation of Aβ and the responsiveness of TAU to Aβ are affected by neuronal cell type, with rostral neurons being more sensitive than caudal neurons. Thus, cell-autonomous factors may in part dictate the pattern of selective regional vulnerability in human neurons in AD.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Muratore CR,Zhou C,Liao M,Fernandez MA,Taylor WM,Lagomarsino VN,Pearse RV 2nd,Rice HC,Negri JM,He A,Srikanth P,Callahan DG,Shin T,Zhou M,Bennett DA,Noggle S,Love JC,Selkoe DJ,Young-Pearse TL

doi

10.1016/j.stemcr.2017.10.015

subject

Has Abstract

pub_date

2017-12-12 00:00:00

pages

1868-1884

issue

6

issn

2213-6711

pii

S2213-6711(17)30470-8

journal_volume

9

pub_type

杂志文章

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