Amyloid-?42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer's disease.
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ABSTRACT:
SUBMITTER: Kwak SS
PROVIDER: S-EPMC7070004 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer's disease.
Kwak Sang Su SS Washicosky Kevin J KJ Brand Emma E von Maydell Djuna D Aronson Jenna J Kim Susan S Capen Diane E DE Cetinbas Murat M Sadreyev Ruslan R Ning Shen S Bylykbashi Enjana E Xia Weiming W Wagner Steven L SL Choi Se Hoon SH Tanzi Rudolph E RE Kim Doo Yeon DY
Nature communications 20200313 1
The relationship between amyloid-β (Aβ) species and tau pathology in Alzheimer's disease (AD) is not fully understood. Here, we provide direct evidence that Aβ42/40 ratio, not total Aβ level, plays a critical role in inducing neurofibrillary tangles (NTFs) in human neurons. Using 3D-differentiated clonal human neural progenitor cells (hNPCs) expressing varying levels of amyloid β precursor protein (APP) and presenilin 1 (PS1) with AD mutations, we show that pathogenic tau accumulation and aggreg ...[more]
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