Cortical biopsy in Alzheimer's disease: Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations

The Intraventricular Bethanecol Study Group

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

Neurochemical assessments were performed on biopsy samples taken from the right frontal lobe of patients diagnosed with Alzheimer's disease (AD), before the implantation of a ventricular catheter and pump assembly for the infusion of bethanechol chloride as an experimental therapy. The pathologically diagnosed patients with AD (n = 35; mean age, 67 ± 1.5 yr) were compared with a group of samples from normal age‐equivalent autopsied controls (n = 22; mean age, 68 ± 2 yr) and autopsied AD brains (n = 11; mean age, 73 ± 2 yr). Samples were assayed for choline acetyltransferase (ChAT), acetylcholinesterase, binding to {3H}quinuclidinyl benzilate as an index of total muscarinic cholinergic binding, and [3H}pirenzepine binding as an index of Ml cholinergic receptor subtype binding. Mean levels of ChAT activity were decreased in the biopsied patients to 36% of age‐matched autopsied controls. The loss of ChAT activity correlated significantly with the Mini‐Mental State Examination, an index of global cognitive function. Mean ChAT activity in autopsied AD cortex was further decreased compared with controls, indicating continuous decline through the course of the disease. Acetylcholinesterase followed a similar, less dramatic decline. No differences were found in {3H}quinuclidinyl benzilate binding or {3H}pirenzepine binding between biopsied and autopsied controls. Neuritic plaque counts did not correlate with either the Mini‐Mental State Examination or ChAT activity in the biopsy specimens. The correlation of cortical ChAT activity with degree of dementia, although considerably weaker than those of cortical synaptic density with dementia, is the first demonstration of such a relationship in biopsied patients, and suggests another reason why the AD brain may be unresponsive to presynaptic cholinergic manipulations or attempts at enhancement.

Original languageEnglish (US)
Pages (from-to)625-632
Number of pages8
JournalAnnals of Neurology
Volume32
Issue number5
DOIs
StatePublished - Jan 1 1992

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Choline O-Acetyltransferase
Alzheimer Disease
Biopsy
Quinuclidinyl Benzilate
Cholinergic Agents
Pirenzepine
Acetylcholinesterase
Dementia
Bethanechol
Infusion Pumps
Investigational Therapies
Amyloid Plaques
Brain
Frontal Lobe
Cholinergic Receptors
Cognition
Catheters

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

@article{9b75fc2b1f6a4e7490a9d6ae13a30821,
title = "Cortical biopsy in Alzheimer's disease: Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations",
abstract = "Neurochemical assessments were performed on biopsy samples taken from the right frontal lobe of patients diagnosed with Alzheimer's disease (AD), before the implantation of a ventricular catheter and pump assembly for the infusion of bethanechol chloride as an experimental therapy. The pathologically diagnosed patients with AD (n = 35; mean age, 67 ± 1.5 yr) were compared with a group of samples from normal age‐equivalent autopsied controls (n = 22; mean age, 68 ± 2 yr) and autopsied AD brains (n = 11; mean age, 73 ± 2 yr). Samples were assayed for choline acetyltransferase (ChAT), acetylcholinesterase, binding to {3H}quinuclidinyl benzilate as an index of total muscarinic cholinergic binding, and [3H}pirenzepine binding as an index of Ml cholinergic receptor subtype binding. Mean levels of ChAT activity were decreased in the biopsied patients to 36{\%} of age‐matched autopsied controls. The loss of ChAT activity correlated significantly with the Mini‐Mental State Examination, an index of global cognitive function. Mean ChAT activity in autopsied AD cortex was further decreased compared with controls, indicating continuous decline through the course of the disease. Acetylcholinesterase followed a similar, less dramatic decline. No differences were found in {3H}quinuclidinyl benzilate binding or {3H}pirenzepine binding between biopsied and autopsied controls. Neuritic plaque counts did not correlate with either the Mini‐Mental State Examination or ChAT activity in the biopsy specimens. The correlation of cortical ChAT activity with degree of dementia, although considerably weaker than those of cortical synaptic density with dementia, is the first demonstration of such a relationship in biopsied patients, and suggests another reason why the AD brain may be unresponsive to presynaptic cholinergic manipulations or attempts at enhancement.",
author = "{The Intraventricular Bethanecol Study Group} and DeKosky, {Dr Steven T.} and Robert Harbaugh and Schmitt, {Frederick A.} and Bakay, {Roy A.E.} and Chui, {Helena Chang} and Knopman, {David S.} and Reeder, {Teddi M.} and Shetter, {Andrew G.} and Senter, {Howard J.} and Markesbery, {William R.}",
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Cortical biopsy in Alzheimer's disease : Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations. / The Intraventricular Bethanecol Study Group.

In: Annals of Neurology, Vol. 32, No. 5, 01.01.1992, p. 625-632.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cortical biopsy in Alzheimer's disease

T2 - Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations

AU - The Intraventricular Bethanecol Study Group

AU - DeKosky, Dr Steven T.

AU - Harbaugh, Robert

AU - Schmitt, Frederick A.

AU - Bakay, Roy A.E.

AU - Chui, Helena Chang

AU - Knopman, David S.

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AU - Senter, Howard J.

AU - Markesbery, William R.

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