Possible role of scavenger receptor SRCL in the clearance of amyloid-beta in Alzheimer's disease.
Accumulation of beta-amyloid protein (Abeta) in the brain is a hallmark of Alzheimer's disease (AD), and Abeta-mediated pathogenesis could result from increased production of Abeta or insufficient Abeta clearance by microglia, astrocytes, or the vascular system. Cell-surface receptors, such as scavenger receptors, might play a critical role in the binding and clearing of Abeta; however, the responsible receptors have yet to be identified. We show that scavenger receptor with C-type lectin (SRCL), a member of the scavenger receptor family containing coiled-coil, collagen-like, and C-type lectin/carbohydrate recognition domains, is expressed in cultured astrocytes and microglia. In contrast to the low expression of SRCL in the wild-type mouse brain, in a double transgenic mouse model of AD (Tg-APP/PS1), immunohistochemistry showed that SRCL was markedly induced in Abeta-positive astrocytes and Abeta-positive vascular/perivascular cells, which are associated closely with cerebral amyloid angiopathy. In patients with AD, the distribution of SRCL was similar to that seen in the Tg-APP/PS1 temporal cortex. The presence of a large number of SRCL/Abeta double-positive particles in the intracellular compartments of reactive astrocytes and vascular/perivascular cells in Tg-APP/PS1 mice and AD patients suggests a role for SRCL in Abeta clearance. Moreover, CHO-K1 cells transfected with SRCL isoforms were found to bind fibrillar Abeta(1-42). These findings suggest that SRCL could be the receptor involved in the binding or clearing of Abeta by glial and vascular/perivascular cells in AD.
Nakamura
Kenji
K
Department of Biochemistry andMolecular Biology, Division of Molecular Regenerative Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. nakamura@onbich.med.osaka-u.ac.jp
Ohya
Wakana
W
Funakoshi
Hiroshi
H
Sakaguchi
Gaku
G
Kato
Akira
A
Takeda
Masatoshi
M
Kudo
Takashi
T
Nakamura
Toshikazu
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000925:Anticoagulants / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D037222:Collectins / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D004347:Drug Interactions; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051116:Receptors, Scavenger / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D016229:Amyloid beta-Peptides; D000925:Anticoagulants; C422442:COLEC12 protein, human; D037222:Collectins; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D012333:RNA, Messenger; D051116:Receptors, Scavenger; C007789:fucoidan