F. Boissiere et al., TRK NEUROTROPHIN RECEPTORS IN CHOLINERGIC NEURONS OF PATIENTS WITH ALZHEIMERS-DISEASE, Dementia and geriatric cognitive disorders, 8(1), 1997, pp. 1-8
Besides cortical pathology, Alzheimer's disease (AD) is characterized
by a loss of cholinergic neurons in the basal forebrain but not in the
caudate nucleus, putamen or mesencephalon. Since cholinergic neurons
which degenerate in AD are sensitive to nerve growth factor (NGF), a l
ink between NGF sensitivity and the vulnerability of cholinergic neuro
ns has been suspected. Levels of NGF are not altered in patients with
AD, however. Thus, cholinergic nerve cell death in AD could result fro
m a deficiency in NGF receptors. Using sequential immunohistochemistry
with antibodies that recognize preferentially TrkA, the specific rece
ptor for NGF, and with antibodies directed against choline acetyltrans
ferase we analyzed the expression of neurotrophin receptors in choline
rgic neurons from control and AD brains. TrkA was expressed on choline
rgic neurons of the striatum and nucleus basalis of Meynert but not on
those of the mesencephalon. In AD patients, the number of neurons exp
ressing TrkA was markedly decreased in the nucleus basalis of Meynert,
very likely as a consequence of cholinergic neuronal loss. No loss of
TrkA-positive neurons was observed in the striatum. Taken in conjunct
ion with our previously published report of loss of high-affinity NGF
binding in the striatum of AD patients, our results suggest a reduced
expression of TrkA, the specific receptor for NGF, on striatal choline
rgic neurons in AD. The loss of neurotrophin receptors may contribute
to the alteration of cholinergic neurons occurring in AD.