Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer's disease
Year: 2020
Type: article
Study design: Observational Study
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.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.12104
Authors: Chia‐Chen Liu, Yu Yamazaki, Michael G. Heckman, Yuka A. Martens, Lin Jia, Akari Yamazaki, Nancy N. Diehl, Jing Zhao, Na Zhao, Michael DeTure, Mary D. Davis, Lindsey M. Felton, Wenhui Qiao, Yonghe Li, Hongmei Li, Yuan Fu, Na Wang, Melissa Wren, Tomonori Aikawa, Marie‐Louise Holm, Hiroshi Oue, Cynthia Linares, Mariet Allen, Minerva M. Carrasquillo, Melissa E. Murray, Ronald C. Petersen, Nilüfer Ertekin‐Taner, Dennis W. Dickson, Takahisa Kanekiyo, Guojun Bu
Institutions: Mayo Clinic, Mayo Clinic in Florida
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Awards: G1269895679, G1496554343, G1897963517, Pathogenic effects of plasma ApoE on CNS function and Alzheimer's disease, Integrative translational discovery of vascular risk factors in aging and dementia, Brain Neurotropic Growth Factor Delivery to Prevent and Treat Alzheimer's Disease, G261300933, ApoE pathway in cerebrovascular Aβ clearance in Alzheimer's disease, ApoE pathway in cerebrovascular Aβ clearance in Alzheimer's disease, G2908616768, G413369726, Clinicopathologic and Neuroimaging Differences in Alzheimer's Disease Variants, G5056103449, Microglial apoE in neuroinflammation and Alzheimer's disease, G6655833625, ApoE isoform-specific therapy for Alzheimer disease, Regional, Synaptic, Cellular Modulation of Abeta Metabolism, Mayo Alzheimer's Disease Research Center
OpenAlex ID: W3081167906