Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: differential neuronal and astroglial pathology.
Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common forms of dementia in the elderly. The neuropathology of AD and DLB is related to cholinergic dysfunctions, and both alpha4 and alpha7 nicotinic acetylcholine receptor (nAChR) subunits are decreased in several brain areas in both diseases. In this immunohistochemical study, we compared neuronal and astroglial alpha4 and alpha7 subunits in AD, DLB and age-matched controls in the hippocampal formation. The numbers of alpha4 reactive neurons were decreased in layer 3 of the entorhinal cortex of AD and DLB, whereas those of alpha7 reactive neurons were decreased in layer 2 of the subiculum of AD and DLB and in layer 3 of the entorhinal cortex of DLB. In contrast, the intensity of alpha7 reactive neuropil was significantly higher in AD than in controls or DLB in a number of areas of the hippocampus (CA3/4 and stratum granulosum), subiculum and entorhinal cortex. An increase in alpha7 immunoreactivity in AD was also associated with astrocytes. The number of astrocytes double-labelled with alpha7 and glial fibrillary acidic protein (GFAP) antibodies was increased in most areas of the hippocampus and entorhinal cortex in AD compared with controls and DLB. Increased astrocyte alpha7 nAChRs in AD may be associated with inflammatory mechanisms related to degenerative processes specific to this disease.
Centre Development in Clinical Brain Aging, MRC Building, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, UK.
Thanasak
T
Teaktong
Alison J
AJ
Graham
Jennifer A
JA
Court
Robert H
RH
Perry
Evelyn
E
Jaros
Mary
M
Johnson
Ros
R
Hall
Elaine K
EK
Perry
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D016022:Case-Control Studies; D002452:Cell Count / Q000379:methods; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D005904:Glial Fibrillary Acidic Protein; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor