High selective expression of alpha7 nicotinic receptors on astrocytes in the brains of patients with sporadic Alzheimer's disease and patients carrying Swedish APP 670/671 mutation: a possible association with neuritic plaques.
In the present study, we have investigated the expression of nicotinic acetylcholine receptors (nAChRs) on astrocytes and neurons in the hippocampus and temporal cortex of subjects carrying the Swedish amyloid precursor protein (APP) 670/671 mutation (APPswe), patients with sporadic Alzheimer's disease (AD), and age-matched control subjects. Significant increases in the total numbers of astrocytes and of astrocytes expressing the alpha7 nAChR subunit, along with significant decreases in the levels of alpha7 and alpha4 nAChR subunits on neurons, were observed in the hippocampus and temporal cortex of both APPswe and sporadic AD brains. Both of these phenomena were more pronounced in APPswe than sporadic AD cases. Furthermore, the number of [(125)I]alpha-BTX binding sites (alpha7 nAChR) in the temporal cortex of the APPswe brain was significant lower than in the younger control group, reflecting the lower neuronal level of alpha7 nAChR. The increase in the level of expression of alpha7 nAChR on astrocytes was positively correlated with the extent of neuropathological alternations, especially the number of neuritic plaques, in the AD brain. The elevated expression of alpha7 nAChR on astrocytes might participate in Abeta cascade and formation of neuritic plaques, thereby playing an important role in the pathogenesis of AD.
Yu
Wen-Feng
WF
Division of Molecular Neuropharmacology, Neurotec Department, Karolinska Institutet, Karolinska University Hospital Huddinge, B84, S-141 86 Stockholm, Sweden.
Guan
Zhi-Zhong
ZZ
Bogdanovic
Nenad
N
Nordberg
Agneta
A
D000109:Acetylcholine / Q000378:metabolism; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D058225:Plaque, Amyloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013548:Sweden; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000109:Acetylcholine; D016564:Amyloid beta-Protein Precursor; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human