Abstract
INTRODUCTION
We investigated the specific factors driving abnormal angiogenesis in Alzheimer’s disease (AD) and its role in cerebrovascular lesions and neurodegeneration.
METHODS
We assessed cerebrovascular pathologies, amyloid-beta (Aβ), and tau pathologies in post mortem human brains and detected 12 angiogenic factors in cerebrospinal fluid (CSF) from the China Aging and Neurodegenerative Disease Initiative (CANDI) cohort.
RESULTS
We observed severe blood-brain barrier damage and elevated levels of the vascular marker CD31 in human AD brains, which had a stronger correlation with tau pathology than Aβ pathology. Consistently, only CSF pTau181 showed positive associations with CSF angiogenesis factors (soluble vascular endothelial growth factor receptor 2 [sVEGFR2], VEGF-C, VEGF-D, placental growth factor [PLGF], Angiopoietin2, and Serpin E1), but not CSF Aβ42/40. Additionally, higher levels of CSF sVEGFR1, soluble Tyrosine-protein kinase receptor 2 [sTIE2], PLGF, and interleukin 8 [IL8], as well as lower levels of CSF urokinase-type plasminogen activator [uPA], were associated with worsen cerebrovascular pathologies and neurodegeneration.
DISCUSSION
Our findings indicate that tau pathology may play a critical role in pathological angiogenesis, contributing to cerebrovascular lesions and neurodegeneration in AD.
HIGHLIGHTS
BBB damage and elevated vascular marker CD31 in human AD brains had a stronger correlation with tau pathology than Aβ pathology.
CSF pTau181 mediated the effect of CSF Aβ42/40 on CSF sVEGFR1 and sTIE2.
Only CSF pTau181 showed positive associations with sVEGFR2, VEGF-C, VEGF-D, PLGF, Angiopoietin2, and Serpin E1.
Higher sVEGFR1, sTIE2, PLGF, and IL8, and lower uPA in CSF, were associated with cerebrovascular pathologies and neurodegeneration.
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This post is Copyright: Feng Gao,
Yaxi Zhan,
Qiong Wang,
Mengguo Zhang,
Linbin Dai,
Yong Shen | January 8, 2025