Phil B.FontanarosaMD, Interim CoeditorIndividualAuthorMargaret A.WinkerMD, Deputy EditorIndividualAuthorStephenLurieMD PhD, Fishbein FellowIndividualAuthor
In Reply: Drs Bartus and Emerich state, "In
fact, ChAT can be inhibited up to 90% with no measurable effects on acetylcholine
synthesis or release." One can extrapolate from this point that the smaller
reductions in ChAT and AChE activity that were observed in the early and mildly
impaired patients with AD whom we studied would be unlikely to produce a deficit
in cholinergic neurotransmission.
Bartus and Emerich also point to the plethora of experiments in animal
model systems (some of which have been contributed by our group), showing
that deficits in forebrain cholinergic systems can result in significant learning
and memory deficits. Although some studies have questioned the validity of
these findings,1,2 we agree
that manipulations that adversely affect the forebrain cholinergic system
can impair learning, memory, and cognition. However, this fact cannot be interpreted
to mean that all cognitive deficits result from forebrain cholinergic system
dysfunction. It is quite possible that the dysfunction in early AD has its
origin in something other than the cholinergic system. The contention that
it is possible that cholinergic system deficits occur in AD "well in advance
of the death of cholinergic neurons" is a hypothesis that must be tested.
That such a state in animal model systems can produce cognitive deficits does
not obligate it to occur in AD, and the results of our studies, although not
definitive in this regard, cast doubt about this contention.
Davis KL, Marin D, Purohit DP, Perl D, Lantz M, Austin G, Haroutunian V. Cholinergic Markers in Alzheimer Disease—Reply. JAMA. 1999;282(23):2208-2209. doi:10-1001/pubs.JAMA-ISSN-0098-7484-282-23-jbk1215