A brain regional analysis of morphologic and cholinergic abnormalities in Alzheimer's disease
G. S. Zubenko, J. Moossy, A. J. Martinez, G. R. Rao, U. Kopp and I. Hanin
Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213.
In the brains of 21 patients with Alzheimer's disease (AD) and 10
nondemented controls, senile plaques (SPs), neurofibrillary tangles (NFTs),
and three indexes of cholinergic function were quantified in the middle
frontal (MF) and superior temporal (ST) cortex, the entorhinal cortex
(HEN), and the prosubiculum (HPR) of the hippocampus. Control brains
contained few SPs without preferential distribution in any of the brain
regions examined, while NFTs were found almost exclusively in the HPR. In
brains from patients with AD, an inverse relationship of SPs and NFTs was
found in the brain regions examined; SPs were preferentially in the
neocortex and NFTs preferentially in the hippocampus. The specific
activities of choline acetyltransferase and acetylcholinesterase were
reduced in all regions examined, while no significant change in the density
of muscarinic binding sites was observed in any region. Numerous NFTs were
associated with an earlier age at onset, while the presence of SPs was
related to the cholinergic deficit in AD. Earlier-onset (less than 67
years) AD was also associated with a qualitative difference in the regional
distribution of NFTs compared with cases with a later onset. In the latter
group, most NFTs were observed in the hippocampus, a distribution pattern
similar to that observed with normal aging. In AD cases with an earlier
onset, NFTs were more globally distributed in the neocortex and allocortex.
