Journal of Neuroscience, Vol 9, 2710-2717, Copyright © 1989 by Society for Neuroscience
Alzheimer's disease antibodies bind specifically to a neurofilament protein in Torpedo cholinergic neurons
J Chapman, O Bachar, AD Korczyn, E Wertman and DM Michaelson
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Alzheimer's disease (AD) is characterized by neurofibrillary tangles and
neuritic plaques and by the degeneration of central cholinergic neurons.
Recent studies indicated the presence of antibodies in the sera and
cerebrospinal fluid of AD patients which react with neuronal tissue and
which recognize cholinergic neurons. In order to identify the cholinergic
antigens against which the AD antibodies are directed, we have recently
used the purely cholinergic electromotor neurons of the electric fish
Torpedo which are chemically homogenous and cross- react antigenically with
mammalian cholinergic neurons. This study revealed that immunoglobulins
(IgG) from sera of AD patients bind specifically to an antigen in Torpedo
electromotor neurons with an apparent molecular weight of 200 kDa. In the
present report we attempt to characterize this antigen. The similarity in
size of this protein to that of the heavy neurofilament subunit (NF-H) and
the association of neurofilaments with plaques and tangles prompted us to
examine the possibility that it is a neurofilament protein. Our findings
show that IgG from sera of AD patients bind to the NF-H protein of Torpedo
cholinergic neurons. Comparison of the binding of AD and control IgG to
Torpedo cholinergic NF-H revealed that AD IgG bind to this neurofilament
protein more readily than do control IgG. In contrast, AD and control IgG
bind similarly to NF-H obtained from the chemically heterogenous Torpedo
spinal cord and rat brain. These findings suggest that AD sera contain a
repertoire of anti-NF-H IgG and that a subpopulation of these antibodies
whose levels are significantly elevated in AD binds to epitopes highly
enriched in Torpedo cholinergic NF-H.(ABSTRACT TRUNCATED AT 250 WORDS)