Unknown

Dataset Information

0

Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer's disease.


ABSTRACT:

Introduction

Cerebrovascular pathologies including cerebral amyloid angiopathy (CAA) and blood-brain barrier (BBB) dysregulation are prominent features in the majority of Alzheimer's disease (AD) cases.

Methods

We performed neuropathologic and biochemical studies on a large, neuropathologically confirmed human AD cohort (N = 469). Amounts of endothelial tight junction proteins claudin-5 (CLDN5) and occludin (OCLN), and major AD-related molecules (amyloid beta [Aβ40], Aβ42, tau, p-tau, and apolipoprotein E) in the temporal cortex were assessed by ELISA.

Results

Higher levels of soluble tau, insoluble p-tau, and apolipoprotein E (apoE) were independently correlated with lower levels of endothelial tight junction proteins CLDN5 and OCLN in AD brains. Although high Aβ40 levels, APOE ε4, and male sex were predominantly associated with exacerbated CAA severity, those factors did not influence tight junction protein levels.

Discussion

Refining the molecular mechanisms connecting tau, Aβ, and apoE with cerebrovascular pathologies is critical for greater understanding of AD pathogenesis and establishing effective therapeutic interventions for the disease.

SUBMITTER: Liu CC 

PROVIDER: S-EPMC8103951 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer's disease.

Liu Chia-Chen CC   Yamazaki Yu Y   Heckman Michael G MG   Martens Yuka A YA   Jia Lin L   Yamazaki Akari A   Diehl Nancy N NN   Zhao Jing J   Zhao Na N   DeTure Michael M   Davis Mary D MD   Felton Lindsey M LM   Qiao Wenhui W   Li Yonghe Y   Li Hongmei H   Fu Yuan Y   Wang Na N   Wren Melissa M   Aikawa Tomonori T   Holm Marie-Louise ML   Oue Hiroshi H   Linares Cynthia C   Allen Mariet M   Carrasquillo Minerva M MM   Murray Melissa E ME   Petersen Ronald C RC   Ertekin-Taner Nilüfer N   Dickson Dennis W DW   Kanekiyo Takahisa T   Bu Guojun G  

Alzheimer's & dementia : the journal of the Alzheimer's Association 20200822 10


<h4>Introduction</h4>Cerebrovascular pathologies including cerebral amyloid angiopathy (CAA) and blood-brain barrier (BBB) dysregulation are prominent features in the majority of Alzheimer's disease (AD) cases.<h4>Methods</h4>We performed neuropathologic and biochemical studies on a large, neuropathologically confirmed human AD cohort (N = 469). Amounts of endothelial tight junction proteins claudin-5 (CLDN5) and occludin (OCLN), and major AD-related molecules (amyloid beta [Aβ40], Aβ42, tau, p-  ...[more]

Similar Datasets

| S-EPMC8128342 | biostudies-literature
| S-EPMC10018855 | biostudies-literature
| S-EPMC6390363 | biostudies-literature
| S-EPMC9420012 | biostudies-literature
| S-EPMC11795418 | biostudies-literature
| S-EPMC11834354 | biostudies-literature
| S-EPMC4835519 | biostudies-literature
| S-EPMC6217595 | biostudies-literature
| S-EPMC7093966 | biostudies-literature
| S-EPMC8094282 | biostudies-literature