Could Serum Antibody to Poly(ADP-Ribose) and/or Histone HI Be Marker for Senile Dementia of Alzheimer Type?

摘要

Poly(ADP-ribosyl)ation has been focused on ischemic injury in the brain in relation to Alzheimer's disease (AD). We have measured IgG antibodies against poly adenosine diphosphate-ribose (pADPR) as well as histone HI (HI) in 26 patients with either AD or with senile dementia of Alzheimer type (SDAT), and found that 80.7% (21/26) were positive for anti-pADPR IgG antibodies. Anti-Hl IgG antibodies were less positive (57.6%) (15/26) than anti-pADPR IgG antibodies, however, titers of both antibodies were well correlated (r = 0.768). Meanwhile, similar studies on 32 patients with systemic lupus erythematosus (SLE) who were positive for anti-pADPR antibody showed poor correlation (r = 0.184) and the difference in the correlation was statistically significant (r < 0.01). It is worthy of remark that anti-double-stranded (ds) DNA antibody, which is the hallmark of SLE, was negative in all dementia patients. Together with the findings that major subclass in dementia is both IgGl and IgG2 and that in SLE was IgG2, the mode of production of anti-pADPR antibody in AD and SDAT is under different regulation mechanisms from that in SLE. Given the evidence that major target for ADP-ribosylation is HI molecule, the association between anti-pADPR and anti-Hl in AD/SDAT makes sense and supports the concept that modification of proteins renders them immunogenic. Whatever the regulation is, parallel assay of two antibodies above would be of use not only for monitoring the disease process but also as a prodrome for possible subsets of SDAT and AD.