Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals.

Active immunization with the human amyloid peptide (Abeta42) or passive immunization with anti-Abeta42 antibodies protects mice that express a mutant human amyloid precursor protein (APP) transgene from cerebral amyloid deposits. If anti-Abeta42 antibodies protect APP-transgenic mice, a model of Alzheimer's disease (AD), a high titer of anti-Abeta42 antibodies may protect humans from AD. The titer of anti-Abeta42 antibodies in serum from individuals with and without late onset AD was measured using an ELISA. The titer of Ig (IgM, IgG and IgA) and IgG anti-Abeta42 peptide antibodies was significantly higher in serum from elderly controls than AD patients. Furthermore, IgG but not Ig anti-Abeta42 antibodies distinguished sera from AD patients and elderly controls that did not have the apolipoprotein E4 allele. The low titer of anti-Abeta42 antibodies in AD patients does not reflect the well-established, age-associated defect in the antibody response to most protein antigens, as there was no positive correlation between the serum titer of anti-Abeta42 antibodies and anti-influenza hemagglutinin antibodies induced by influenza vaccine in elderly humans. The lower titer of serum anti-Abeta42 peptide antibodies in AD patients may reflect the reported specific impairment of helper T cell activity for B cells that produce anti-amyloid-beta42 peptide antibodies in APP-transgenic mice.