Scavenger receptor a deficiency accelerates cerebrovascular amyloidosis in an animal model

Veronica Lifshitz, Ronen Weiss, Hilit Levy, Dan Frenkel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Cerebrovascular amyloidosis caused by amyloid accumulation in blood vessel walls may lead to hemorrhagic stroke and cognitive impairment. Expression of TGF-β1 under glial fibrillary acidic protein promoter in mice leads to age-related deposition of amyloid, including β-amyloid (Aβ), around cerebral blood vessels, leading to vascular pathology starting at age of 7 months. We have recently shown the important role of macrophages in clearing cerebrovascular amyloid. Scavenger receptor A (SRA) is a multi-ligand and multifunctional receptor expressed on macrophages, and it has been suggested to play a role in meditating phagocytosis of different types of antigens. We investigated the role of SRA in mediating cerebrovascular amyloid clearance. We bred TGF-β1 mice with SRA-/- mice and discovered that TGF-β1/SRA-/- mice showed cerebrovascular pathology at an earlier age (3 months) compared with TGF-β1 mice. Furthermore, SRA deficiency in macrophages led to impaired clearing of congophilic cerebrovascular amyloid from amyloid precursor protein mouse model and led to reduced phagocytosis of both soluble and insoluble Aβ in vivo as compared with macrophages from wild-type mice. Our findings demonstrate the important role of SRA in cerebrovascular amyloid pathology and suggest targeting SRA for future diagnostic and therapeutic approaches for cerebral amyloid angiopathy.

Original languageEnglish
Pages (from-to)198-203
Number of pages6
JournalJournal of Molecular Neuroscience
Volume50
Issue number1
DOIs
StatePublished - May 2013

Funding

FundersFunder number
Alzheimer's AssociationNIRG-11-205535
Israel Science Foundation

    Keywords

    • Alzheimer's disease
    • Cerebrovascular amyloid angiopathy
    • Scavenger receptor A
    • TGF-β1
    • β-amyloid

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