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 pathomechanism of sporadic Alzheimer disease (AD) has been suggested by evidence for activated microgila and the potential therapeutic benefit of anti-inflammatory medication. Objective: To define a possible role for IgG in the immune/inflammatory process of AD in humans, we assayed the ability of IgG samples from patients with AD to target the injury to cholinergic neurons in rat basal forebrain in vivo. Design: IgG purified from the serum or plasma from patients with AD and patients with other neurological disease who were used as control (DC) patients was injected stereotaxically into the medial septum of adult rats. Four weeks later coronal sections of the whole medial septum-diagonal bands of Broca region were immunostained for choline acetyltransferase (ChAT) to identify cholinergic neuronal cells. Setting: University medical centers. Patients: Blood samples were collected from 8 patients with probable and definite AD and from 6 age-matched DC patients. Main Outcome Measure: Detection of changes in the number of ChAT immunopositive 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 the whole medial septum-diagonal bands of Broca region compared with IgGs from 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 A.D can target a stereotaxically induced immmune/inflammatory injury to cholinergic neurons in the rat basal forebrain in vivo.