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June 1989

A Brain Regional Analysis of Morphologic and Cholinergic Abnormalities in Alzheimer's Disease

Author Affiliations

From the Western Psychiatric Institute and Clinic (Dr Zubenko and Ms Kopp), the Department of Psychiatry (Dr Zubenko and Ms Kopp), and the Division of Neuropathology, Department of Pathology (Drs Moossy, Martinez, and Rao), University of Pittsburgh (Pa) School of Medicine; the Department of Biological Sciences, Mellon Institute, Carnegie-Mellon University, Pittsburgh, Pa (Dr Zubenko); and the Department of Pharmacology and Experimental Therapeutics, Stritch School of Medicine, Loyola University, Maywood, Ill (Dr Hanin).

Arch Neurol. 1989;46(6):634-638. doi:10.1001/archneur.1989.00520420054022

• 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 (<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.