title: Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is characterized by neurofibrillary tangles and by the accumulation of beta-amyloid (Abeta) 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 Abeta 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 Abeta 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 Abeta load in the cortex, with the severity of CAA, and with ApoE epsilon4 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 Abeta 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.
authors.affiliation: The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, Sun City, AZ 85351, USA. alex.roher@sunhealth.org
authors.forename: Alex E
authors.initials: AE
authors.lastname: Roher
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Kuo
authors.forename: Chera
authors.initials: C
authors.lastname: Esh
authors.forename: Carmen
authors.initials: C
authors.lastname: Knebel
authors.forename: Nicole
authors.initials: N
authors.lastname: Weiss
authors.forename: Walter
authors.initials: W
authors.lastname: Kalback
authors.forename: Dean C
authors.initials: DC
authors.lastname: Luehrs
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Childress
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Roy O
authors.initials: RO
authors.lastname: Weller
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Kokjohn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis; D001921:Brain / Q000098:blood supply / Q000473:pathology; D001923:Brain Chemistry; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000473:pathology; D045604:Extracellular Fluid; D005110:Extracellular Space; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008578:Meninges / Q000098:blood supply* / Q000473:pathology; D008875:Middle Aged
chemical_list: D016229:Amyloid beta-Peptides