Autoimmune responses to amyloid structures of Abeta(25-35) peptide and human lysozyme in the serum of patients with progressive Alzheimer's disease.
We have found an increased level of serum antibodies to the prefibrillar structures of both Abeta(25-35) peptide and human lysozyme in Alzheimer's disease (AD) patients compared to age-matched controls, indicating that autoimmunity is implicated in AD. In the serum of AD patients with a long-term duration (>15 years) the titer of serum antibodies to aggregates of Abeta(25-35) peptide increased by approximately 5-fold, whilst the antibody titer to lysozyme protofilaments decreased by approximately 8-fold compared to patients with AD duration of <5 years. The content of immunoglobulins of the A, G and M types declined, particularly in AD duration of >15 years. An increase in the concentration of immune complexes and higher lysozyme activity was detected in the serum of all patients and this was suggestive of an inflammatory reaction. We propose that the autoimmune response to different amyloid structures in AD can be viewed as a clearance pathway targeting amyloid development. Autoimmune response can be exploited as a marker of ongoing protein aggregation and hence be used as a diagnostic feature of AD.
Gruden
M A
MA
P.K. Anokhin Institute of Normal Physiology, RAS, Moscow, Russia.
Davudova
T B
TB
Malisauskas
M
M
Zamotin
V V
VV
Sewell
R D E
RD
Voskresenskaya
N I
NI
Kostanyan
I A
IA
Sherstnev
V V
VV
Morozova-Roche
L A
LA
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D000682:Amyloid / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001921:Brain / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000175:diagnosis / Q000276:immunology*; D003937:Diagnosis, Differential; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007105:Immune Complex Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood; D008279:Magnetic Resonance Imaging; D008609:Mental Status Schedule; D018625:Microscopy, Atomic Force; D009113:Muramidase / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D012016:Reference Values; D014057:Tomography, X-Ray Computed
D000682:Amyloid; D016229:Amyloid beta-Peptides; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007136:Immunoglobulins; D010446:Peptide Fragments; D009113:Muramidase