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PMID: 18363936 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease.

Brain pathology (Zurich, Switzerland) ·Vol. 18 ·No. 2 ·2008-04-00 ·Pages 253-66

Weller RO, Subash M, Preston SD, Mazanti I, Carare RO

Abstract

Alzheimer's disease is the commonest dementia. One major characteristic of its pathology is accumulation of amyloid-beta (Abeta) as insoluble deposits in brain parenchyma and in blood vessel walls [cerebral amyloid angiopathy (CAA)]. The distribution of Abeta deposits in the basement membranes of cerebral capillaries and arteries corresponds to the perivascular drainage pathways by which interstitial fluid (ISF) and solutes are eliminated from the brain--effectively the lymphatic drainage of the brain. Theoretical models suggest that vessel pulsations supply the motive force for perivascular drainage of ISF and solutes. As arteries stiffen with age, the amplitude of pulsations is reduced and insoluble Abeta is deposited in ISF drainage pathways as CAA, thus, further impeding the drainage of soluble Abeta. Failure of perivascular drainage of Abeta and deposition of Abeta in the walls of arteries has two major consequences: (i) intracerebral hemorrhage associated with rupture of Abeta-laden arteries in CAA; and (ii) Alzheimer's disease in which failure of elimination of ISF, Abeta and other soluble metabolites from the brain alters homeostasis and the neuronal environment resulting in cognitive decline and dementia. Therapeutic strategies that improve elimination of Abeta and other soluble metabolites from the brain may prevent cognitive decline in Alzheimer's disease.

MeSH Terms
Alzheimer Disease/metabolism,pathology,therapy Amyloid beta-Peptides/metabolism Animals Cerebral Amyloid Angiopathy/metabolism,pathology,therapy Drainage/methods Humans
Chemicals
Amyloid beta-Peptides
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Weller Roy O
Clinical Neurosciences, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK. row@soton.ac.uk
Subash Malavika
Preston Stephen D
Mazanti Ingrid
Carare Roxana O
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Article Info
Journal
Brain pathology (Zurich, Switzerland)
Abbr.
Brain Pathol
ISSN
1015-6305
DOI
10.1111/j.1750-3639.2008.00133.x
Email
row@soton.ac.uk
Published
2008-04-00
Pages
253-66
Language
English
Region
Switzerland
NLM ID
9216781
PMCID
PMC8095597
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1750-3639.2008.00133.x PMC Full Text View journal details
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