title: Alzheimer's disease is associated with a selective increase in alpha7 nicotinic acetylcholine receptor immunoreactivity in astrocytes.
abstract: Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common forms of dementia in the elderly associated with cholinergic dysfunction, including reductions in nicotinic acetylcholine receptors (nAChRs). In AD, astrocytes are implicated in the formation of senile plaques, one of the core pathological features. Using immunohistochemistry, we have investigated astrocytic expression of the two major nicotinic receptor alpha subunits in the human hippocampus and entorhinal cortex. alpha7, but not alpha4, subunit immunoreactivity was associated with astrocytes. An increase in the proportion of astrocytes expressing alpha7 immunoreactivity was observed in AD compared with age-matched controls. A similar increase was not evident in DLB. Elevated alpha7 nAChRs on astrocytes in AD may contribute to alterations in calcium homeostasis and nitric oxide production, which in turn could affect beta-amyloid-mediated inflammatory processes in AD.
authors.affiliation: MRC Building, Centre Development in Clinical Brain Aging, Newcastle General Hospital, Newcastle Upon Tyne, UK.
authors.forename: Thanasak
authors.initials: T
authors.lastname: Teaktong
authors.forename: Alison
authors.initials: A
authors.lastname: Graham
authors.forename: Jennifer
authors.initials: J
authors.lastname: Court
authors.forename: Robert
authors.initials: R
authors.lastname: Perry
authors.forename: Evelyn
authors.initials: E
authors.lastname: Jaros
authors.forename: Mary
authors.initials: M
authors.lastname: Johnson
authors.forename: Ros
authors.initials: R
authors.lastname: Hall
authors.forename: Elaine
authors.initials: E
authors.lastname: Perry
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D018728:Entorhinal Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D002118:Calcium; D009569:Nitric Oxide; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human