Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer's disease

Alex E. Roher, Yu Min Kuo, Chera Esh, Carmen Knebel, Nicole Weiss, Walter Kalback, Dean C. Luehrs, Jennifer L. Childress, Thomas G. Beach, Roy O. Weller, Tyler A. Kokjohn

研究成果: Article同行評審

182 引文 斯高帕斯(Scopus)

摘要

Alzheimer's disease (AD) is characterized by neurofibrillary tangles and by the accumulation of β-amyloid (Aβ) peptides in senile plaques and in the walls of cortical and leptomeningeal arteries as cerebral amyloid angiopathy (CAA). There also is a significant increase of interstitial fluid (ISF) in cerebral white matter (WM), the pathological basis of which is largely unknown. We hypothesized that the accumulation of ISF in dilated periarterial spaces of the WM in AD correlates with the severity of CAA, with the total Aβ load in the cortex and with Apo E genotype. A total of 24 AD brains and 17 nondemented age-matched control brains were examined. CAA was seen in vessels isolated from brain by using EDTA-SDS lysis stained by Thioflavin-S. Total Aβ in gray matter and WM was quantified by immunoassay, ApoE genotyping by PCR, and dilatation of perivascular spaces in the WM was assessed by quantitative histology. The study showed that the frequency and severity of dilatation of perivascular spaces in the WM in AD were significantly greater than in controls (P < 0.001) and correlated with Aβ load in the cortex, with the severity of CAA, and with ApoE ε4 genotype. The results of this study suggest that dilation of perivascular spaces and failure of drainage of ISF from the WM in AD may be associated with the deposition of Aβ in the perivascular fluid drainage pathways of cortical and leptomeningeal arteries. This failure of fluid drainage has implications for therapeutic strategies to treat Alzheimer's disease.

原文English
頁(從 - 到)112-122
頁數11
期刊Molecular Medicine
9
發行號3-4
DOIs
出版狀態Published - 2003

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 分子生物學
  • 遺傳學
  • 遺傳學(臨床)

指紋

深入研究「Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer's disease」主題。共同形成了獨特的指紋。

引用此