Association of apolipoprotein J-positive beta-amyloid plaques with dystrophic neurites in Alzheimer's disease brain.
Apolipoprotein J (apoJ), also known as clusterin and SP-40,40, binds soluble beta-amyloid (Abeta and is up-regulated in the Alzheimer's disease (AD) brain. In the present study we classified apoJ-immunopositive Abeta deposits in AD temporal cortex, and found apoJ-immunoreactive plaques were often associated with dystrophic neurites. Quantitative immunohistochemical analysis of five AD brains showed that 29% of Abeta deposited in the parenchyma was associated with apoJ. Of Abeta deposits with apoJ immunopositivity, 71% were associated with phospho-tau-positive dystrophic neurites in the surrounding tissue. Conversely, 64% of phospho-tau-labeled neuritic deposits were labeled with apoJ. ApoJ was found at the core of these deposits, and co-localized with the amyloid staining agent thioflavine-S. To test the direct effects of apoJ on tau metabolism, we treated cells in culture with apoJ-containing conditioned media, and we injected apoJ-containing media into the rat hippocampus. Using both systems, we observed increases in levels of tau and phosphorylated tau. Our findings demonstrate that apoJ immunopositivity strongly correlates with the presence of amyloid and associated neuritic dystrophy in the neuropil of AD temporal cortex, and supports a model where extracellular apoJ facilitates the conversion of diffuse Abeta deposits into amyloid and enhances tau phosphorylation in neurites surrounding these of plaques.
Martin-Rehrmann
M D
MD
Alzheimer Research Unit, 114 16th Street, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Hoe
H-S
HS
Capuani
E M
EM
Rebeck
G W
GW
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D016022:Case-Control Studies; D002452:Cell Count; D002478:Cells, Cultured; D051152:Clusterin; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; C495242:CLU protein, human; C495243:Clu protein, mouse; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; C085348:tau-1 monoclonal antibody