Autoantibodies against beta-amyloid are common in Alzheimer's disease and help control plaque burden.
OBJECTIVE
Active or passive immunization of Alzheimer's disease (AD) patients leads to targeting of beta-amyloid plaques by immunoglobulins (IgG) and their subsequent removal by microglia. Here, we investigate whether naturally occurring autoantibodies to beta-amyloid contribute to beta-amyloid plaque removal in nonimmunized AD patients.


METHODS
We generated an AD tissue microarray with 2,325 tissue specimens from 3 defined central nervous system regions of 48 AD patients and 48 age-matched control patients. Absolute quantification of beta-amyloid, beta-amyloid plaque-bound IgG, and phagocytic, resting, and activated microglia and microhemorrhages was done using a standardized, highly reproducible scoring system.


RESULTS
The majority of neuritic plaques are decorated by IgG. AD patients with prominently IgG-labeled neuritic plaques have a significantly reduced plaque burden and an increase in phagocytic microglia, yet no increase in microhemorrhages.


CONCLUSIONS
Autoantibodies directed against beta-amyloid are common in AD patients and may contribute in controlling plaque burden.
Kellner
Alexander
A
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Matschke
Jakob
J
Bernreuther
Christian
C
Moch
Holger
H
Ferrer
Isidro
I
Glatzel
Markus
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007211:Indoles; D008297:Male; D051379:Mice; D046228:Microarray Analysis / Q000379:methods; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D000097382:CD68 Molecule
D016229:Amyloid beta-Peptides; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D007211:Indoles; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C007293:DAPI