Analysis of the autoimmune response against BP180 in patients with Alzheimer's disease

Current epidemiological studies suggest a significant correlation between Alzheimer's disease (AD) and bullous pemphigoid (BP). However, the autoimmune response against BP180 in patients with AD has not been fully understood. investigated.

We randomly enrolled 48 patients with AD and 50 sex- and age-matched healthy controls. We detected the presence/absence and the level of anti-BP180/BP230 immunoglobulin G (IgG) autoantibodies in the patients' serum to determine whether said antibodies possess reactivity against the BP180 protein in the human brain and skin.

The enzyme-linked immunosorbent assay (ELISA) results revealed that the positive rate of anti-BP180 autoantibodies in patients with AD (23/48, 47.9%) was significantly higher than that in controls (4/50, 8.0%; P<0.0001). These ELISA-positive patients were further examined through immunoblotting. Sera from nine patients with AD (9/23, 39.1%) and one control (1/4, 25.0%) reacted with human cutaneous recombinant full-length BP180 and BP180-noncollagenous 16A (NC16A). Sera from 11 (11/23, 47.8%) patients with AD reacted with a 180-kDa protein from the human brain extract, but none of the controls' sera recognized the corresponding protein band. The majority of the patients in the anti-BP180-positive AD group were men (14/23, 60.9%) who were older (74.0 years) compared with those in the control group (6/25, 24.0%; P<0.05) (72.2 years; P<0.01).

Anti-BP180 autoantibodies are present in AD and recognize human recombinant full-length BP180 and a 180-kDa protein from the human brain extract, suggesting that BP180 is a shared autoantigen in AD and BP and may help clarify the mechanism to explain why a high risk of BP exists in AD. Elderly male patients with AD are significantly more likely to develop BP180 serum autoreactivity compared with other patients with AD.