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.
Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer's disease
Molecular Medicine, 9, (3-4), .
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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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