Stereotaxic injection of IgG from patients with Alzheimer disease initiates injury of cholinergic neurons of the basal forebrain

Context: The participation of an immune/inflammatory process in the pathome chanism of sporadic Alzheimer disease (AD) has been suggested by evidence f or activated microglia and the potential therapeutic benefit of anti-inflam matory medication. Objective: To define a possible role for IgG in the immune/inflammatory pro cess of AD in humans, we assayed the ability of IgG samples from patients w ith AD to target the injury to cholinergic neurons in rat basal forebrain i n vivo. Design: IgG purified from the serum or plasma from patients with AD and pat ients with other neurological disease who were use as control (DC) patients was injected stereotaxically into the medial septum of adult rats. Four we eks later coronal sections of the whole medial septum-diagonal bands of Bro ca region were immunostained for choline acetyltransdferase (ChaT) to ident ify cholinergic neuronal cells. Setting: University medical centers. Patients: Blood samples were collected from 8 patients with probable and de finite AD and from 6 age-matched DC patients. Main Outcome Measure: Detection of changes in the number of ChaT immunoposi tive cell profiles in sections and statistical evaluation. Results: Four weeks after the injections, IgG samples from patients with AD significantly reduced the number of ChaT-immunostained cell profiles in th e whole medial septum-diagonal bands of Broca region compared with IgGs fro m DC patients. Neither DC IgGs nor saline solution significantly decreased the number of ChaT-immunopositive neuronal cell profiles. Conclusion: Data document that IgG from patients with AD can target a stere otaxically induced immune/inflammatory injury to cholinergic neurons in the rat basal forebrain in vivo.