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

Roher, Alex E., Kuo, Yu-Min, Esh, Chera, Knebel, Carmen, Weiss, Nicole, Kalback, Walter, Luehrs, Dean C., Childress, Jennifer L., Beach, Thomas G., Weller, Roy O. and Kokjohn, Tyler A. (2003) Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer's disease Molecular Medicine, 9, (3-4), pp. 112-122.

Record type: Article


Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and by the accumulation of ?-amyloid (A?) 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 A? 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 A? 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 A? load in the cortex, with the severity of CAA, and with ApoE ?4 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 A? 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.

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Published date: 2003


Local EPrints ID: 27703
ISSN: 1076-1551
PURE UUID: 1f0c28e1-f625-4a80-874e-cfb2d63b4ee0

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Date deposited: 28 Apr 2006
Last modified: 17 Jul 2017 16:03

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

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