Decreased Density of Forebrain Cholinergic Neurons and Disintegration of the Spatial Organization of Behavior in Experimental Autoimmune Dementia (EAD)

Experimental autoimmune dementia (EAD) is a rat model designed to examine the potential role of anti‐cholinergic neurons antibodies (Abs) in the neuropathology of Alzheimer's disease (AD) and dementia. We have previously shown that sera of AD and Down's syndrome patients contain Abs which bind specifically to the high molecular weight neurofilament protein (NF‐H) of the purely cholinergic electromotor neurons of Torpedo. Production of such Abs in EAD rats by prolonged immunization with Torpedo cholinergic NF‐H results in the accumulation of IgG in the septum and hippocampus of the immunized rats and in memory deficits. In the present study, we examined immunohistochemically whether the anti‐cholinergic NF‐H immune response of the FAD rats affects their brain cholinergic neurons. In addition, since dementia is associated with severe deterioration in the spatio‐temporal organization of behavior, we examined whether EAD rats also mimic this important feature of dementia. The results obtained show that production in EAD rats of anti‐cholinergic NF‐H Abs similar to those found in AD patients results in a marked decrease in the density of forebrain cholinergic neurons and in derangements in the spatio‐temporal organization of their behavior. These findings may replicate pathogenic processes in AD and support a role for anti‐cholinergic NF‐H Abs in the degeneration of cholinergic neurons in the disease.