@article{804a7f4b79f94299bdc59b04e7f20e24,
title = "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.",
keywords = "Alzheimer's disease, blood-brain barrier, cerebral amyloid angiopathy, tau, tight junction",
author = "Liu, {Chia Chen} and Yu Yamazaki and Heckman, {Michael G.} and Martens, {Yuka A.} and Lin Jia and Akari Yamazaki and Diehl, {Nancy N.} and Jing Zhao and Na Zhao and Michael DeTure and Davis, {Mary D.} and Felton, {Lindsey M.} and Wenhui Qiao and Yonghe Li and Hongmei Li and Yuan Fu and Na Wang and Melissa Wren and Tomonori Aikawa and Holm, {Marie Louise} and Hiroshi Oue and Cynthia Linares and Mariet Allen and Carrasquillo, {Minerva M.} and Murray, {Melissa E.} and Petersen, {Ronald C.} and Nil{\"u}fer Ertekin-Taner and Dickson, {Dennis W.} and Takahisa Kanekiyo and Guojun Bu",
note = "Funding Information: This work was supported by grants from the National Institutes of Health (NIH) (RF1AG051504, a component of the MOVE‐AD Consortium (Molecular Mechanisms of the Vascular Etiology of AD‐Consortium to G.B. and N.E.‐T.; P50AG016574, R37AG027924, R01AG035355, RF1AG046205, and P01NS074969 to G.B.; R01AG051574 to T.K.; U01AG046139 and R01AG061796 to N.E.‐T.; and R01AG054449 to M.E.M.); a Cure Alzheimer's Fund (to G.B.); Florida Department of Health Ed and Ethel Moore Alzheimer's Disease Research Program (7AZ22 to T.K.); NIH grants R21AG057981 and RF1AG062110, Florida Department of Health Ed and Ethel Moore Alzheimer's Disease Research Program (8AZ07), and a grant from the Alzheimer's Association (AARG‐17‐500335) to C.‐C.L. The authors would like to acknowledge the continuous commitment and teamwork offered by Amanda M. Liesinger, Linda G. Rousseau, Ariston L. Librero, Virginia R. Phillips, and Monica Castanedes‐Casey for their dedicated efforts to Mayo Clinic Brain Bank. 2 Funding Information: This work was supported by grants from the National Institutes of Health (NIH) (RF1AG051504, a component of the M2OVE-AD Consortium (Molecular Mechanisms of the Vascular Etiology of AD-Consortium to?G.B. and N.E.-T.; P50AG016574, R37AG027924, R01AG035355, RF1AG046205, and P01NS074969 to G.B.; R01AG051574 to T.K.; U01AG046139 and R01AG061796 to N.E.-T.; and R01AG054449 to M.E.M.); a Cure Alzheimer's Fund (to G.B.); Florida Department of Health Ed and Ethel Moore Alzheimer's Disease Research Program (7AZ22 to T.K.); NIH grants R21AG057981 and RF1AG062110, Florida Department of Health Ed and Ethel Moore Alzheimer's Disease Research Program (8AZ07), and a grant from the Alzheimer's Association (AARG-17-500335) to C.-C.L. The authors would like to acknowledge the continuous commitment and teamwork offered by Amanda M. Liesinger, Linda G. Rousseau, Ariston L. Librero, Virginia R. Phillips, and Monica Castanedes-Casey for their dedicated efforts to Mayo Clinic Brain Bank. Publisher Copyright: {\textcopyright} 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association",
year = "2020",
month = oct,
day = "1",
doi = "10.1002/alz.12104",
language = "English (US)",
volume = "16",
pages = "1372--1383",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "10",
}