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

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.