Alzheimer's disease is associated with a selective increase in alpha7 nicotinic acetylcholine receptor immunoreactivity in astrocytes.
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.
Teaktong
Thanasak
T
MRC Building, Centre Development in Clinical Brain Aging, Newcastle General Hospital, Newcastle Upon Tyne, UK.
Graham
Alison
A
Court
Jennifer
J
Perry
Robert
R
Jaros
Evelyn
E
Johnson
Mary
M
Hall
Ros
R
Perry
Elaine
E
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
D002118:Calcium; D009569:Nitric Oxide; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human