ANTIBODIES TO DIFFERENT ISOFORMS OF THE HEAVY NEUROFILAMENT PROTEIN (NF-H) IN NORMAL AGING AND ALZHEIMERS-DISEASE

Sera of normal controls and of patients with neurological diseases con tain antineurofilament antibodies. Recent studies suggest that biochem ically and immunologically distinct subclasses of neurofilaments occur in different types of neurons. Alzheimer's disease (AD), the major ca use of dementia, is associated with a marked degeneration of brain cho linergic neurons. In the present work we characterized the repertoire and age dependence of antineurofilament antibodies in normal sera and examined whether the degeneration of cholinergic neurons in AD is asso ciated with serum antibodies directed specifically against the neurofi laments of mammalian cholinergic neurons. This was performed by immuno blot assays utilizing neurofilaments from the purely cholinergic bovin e ventral root neurons and from the chemically heterogeneous bovine do rsal root neurons, Antibodies to the heavy neurofilament protein NF-H were detected in normal control sera. Their levels were significantly higher in older (aged 70-79) than in younger (aged 40-59) subjects. Th ese antibodies bound similarly to bovine ventral root and dorsal root NF-H and their NF-H specificity was unchanged during aging. In contras t, the levels of IgG in AD sera that are directed against ventral root cholinergic NF-H were higher than those directed against the chemical ly heterogeneous dorsal root NF-H. Immunoblot experiments utilizing de phosphorylated ventral root and dorsal root NF-H and chymotryptic frag ments of these molecules revealed that AD sera contain a repertoire of antimamalian NF-H IgG. A subpopulation of these antibodies binds to p hosphorylated epitopes that are specifically enriched in ventral root cholinergic NF-H and that are located on the carboxy terminal domain o f this molecule. The level of these anticholinergic NF-H IgG are signi ficantly higher in AD sera than in those of both normal controls and p atients with multi-infarct dementia.