Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer's disease.
Alzheimer's disease
blood-brain barrier
cerebral amyloid angiopathy
tau
tight junction
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
06
07
2019
revised:
05
01
2020
accepted:
15
01
2020
pubmed:
23
8
2020
medline:
28
9
2021
entrez:
23
8
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 32827351
doi: 10.1002/alz.12104
pmc: PMC8103951
mid: NIHMS1693748
doi:
Substances chimiques
Amyloid beta-Peptides
0
Apolipoprotein E4
0
MAPT protein, human
0
Tight Junction Proteins
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1372-1383Subventions
Organisme : NIA NIH HHS
ID : R01 AG035355
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054449
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG051504
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG062110
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG027924
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061796
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG027924
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG046205
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG057981
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG051574
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS074969
Pays : United States
Informations de copyright
© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.
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