Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls.
Antibodies to amyloid beta protein (Abeta) are present naturally or after Abeta vaccine therapy in human plasma. To clarify their clinical role, we examined plasma samples from 113 patients with Alzheimer's disease (AD) and 205 normal controls using the tissue amyloid plaque immunoreactivity (TAPIR) assay. A high positive rate of TAPIR was revealed in AD (45.1%) and age-matched controls (41.2%), however, no significance was observed. No significant difference was observed in the MMS score or disease duration between TAPIR-positive and negative samples. TAPIR-positive plasma reacted with the Abeta40 monomer and dimer, and the Abeta42 monomer weakly, but not with the Abeta42 dimer. TAPIR was even detected in samples from young normal subjects and young Tg2576 transgenic mice. Although the Abeta40 level and Abeta40/42 ratio increased, and Abeta42 was significantly decreased in plasma from AD groups when compared to controls, no significant correlations were revealed between plasma Abeta levels and TAPIR grading. Thus an immune response to Abeta40 and immune tolerance to Abeta42 occurred naturally in humans without a close relationship to the Abeta burden in the brain. Clarification of the mechanism of the immune response to Abeta42 is necessary for realization of an immunotherapy for AD.
Xu
Wuhua
W
Department of Neurology, Neuroscience, Biophysiological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmacy, 2-5-1 Shikatacho, Okayama 700-8558, Japan.
Kawarabayashi
Takeshi
T
Matsubara
Etsuro
E
Deguchi
Kentaro
K
Murakami
Tetsuro
T
Harigaya
Yasuo
Y
Ikeda
Masaki
M
Amari
Masakuni
M
Kuwano
Ryozo
R
Abe
Koji
K
Shoji
Mikio
M
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D008609:Mental Status Schedule; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D012372:ROC Curve; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)