Alzheimer's disease and down's syndrome antibodies bind to the heavy neurofilament protein of cholinergic neurons

There is a growing body of evidence which suggests that immunological mechanisms may play a role in the pathogenesis of Alzheimer's disease (AD). We focused our attention on the cholinergic nervous system and explored whether sera of AD patients contain antibodies (Ab) which bind to specific constituents of cholinergic neurons. Virtually all individuals with Down's syndrome (DS) who survive beyond the age of 30 display brain lesions characteristic of AD. These include senile plaques and neurofibrillary tangles as well as marked degeneration of brain cholinergic neurons. The similarities between the neuropathology and cholinergic deficiencies of AD and DS and the observation that DS is also associated with immunological changes prompted us to examine whether DS sera also contain anticholinergic-neuron Ab and to compare their antigen specificity to that of AD Ab. The AD and DS anticholinergic-neuron Ab and the antigens against which they are directed were detected by immunoblot assays utilizing purely cholinergic neurons isolated from the electromotor system of the electric fish Torpedo and from bovine ventral roots.