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 E.
AU - Schmitt, Frederick A.
AU - Bakay, Roy A.E.
AU - Chui, Helena Chang
AU - Knopman, David S.
AU - Reeder, Teddi M.
AU - Shetter, Andrew G.
AU - Senter, Howard J.
AU - Markesbery, William R.
PY - 1992/11
Y1 - 1992/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0026440987&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026440987&partnerID=8YFLogxK
U2 - 10.1002/ana.410320505
DO - 10.1002/ana.410320505
M3 - Article
C2 - 1360195
AN - SCOPUS:0026440987
SN - 0364-5134
VL - 32
SP - 625
EP - 632
JO - Annals of Neurology
JF - Annals of Neurology
IS - 5
ER -