K. Shiozaki et al., Alterations of muscarinic acetylcholine receptor subtypes in diffuse Lewy body disease: relation to Alzheimer's disease, J NE NE PSY, 67(2), 1999, pp. 209-213
Objectives-Dementia associated with Lewy bodies in cortical and subcortical
areas is classified as dementia of the non-Alzheimer type and termed diffu
se Lewy body disease (DLBD). The generic term "dementia with Lewy bodies (D
LB)" was proposed in the international workshop on Lewy body dementia to in
clude the similar disorders presenting Lewy bodies. In DLB, a lower level o
f choline acetyltransferase (ChAT) activity in the neocortex was found comp
ared with that in Alzheimer's disease. The purpose of the present study was
to determine the total amount of muscarinic acetylcholine receptors (mAChR
s) and relative proportion of each subtype (m1-m4) of mAChRs in the frontal
and temporal cortex of seven DLBD and 11 Alzheimer's disease necropsied br
ains.
Methods-A [H-3]quinuclidinyl benzilate (QNB) binding assay and an immunopre
cipitation assay using subtype-specific antibodies were performed. Each ant
ibody was raised against fusion proteins containing peptides corresponding
to the third intracellular (i3) loops of the respective mAChR subtype.
Results-The total amounts of mAChRs were significantly lower in the prepara
tions of temporal cortices from DLBD and Alzheimer's disease than in those
from dead controls (seven cases). In both diseases, the proportion of the m
3 receptor in the frontal cortex was significantly increased and that of th
e m4 receptor in the temporal cortex was significantly decreased compared w
ith the control specimens. The proportions of the m1 and m2 subtypes were s
ignificantly different in the temporal cortex. The proportion of the m1 rec
eptor was significantly greater in the DLBD brains, whereas that of the m2
receptor was significantly greater in the Alzheimer's disease brains than i
n the controls.
Conclusions-The m1 receptor is the major subtype in the cerebral cortex, an
d m2 is known to be present at presynaptic terminals. The higher proportion
s of m1 in DLBD and m2 in Alzheimer's disease suggest that the manner of de
generation in the cholinergic system is different between the diseases. It
is hypothesised that a severe depletion of presynaptic cholinergic projecti
ve neurons causes the upregulation of m1 receptor in the temporal cortex in
DLBD.