Alpha7 nicotinic acetylcholine receptor expression in Alzheimer's disease: receptor densities in brain regions of the APP(SWE) mouse model and in human peripheral blood lymphocytes.
The brains of people with Alzheimer's disease (AD) display several characteristic pathological features, including deposits (plaques) of beta-amyloid 1-42 (Abeta1-42), intraneuronal accumulations (tangles) of hyperphosphorylated tau, degeneration of the basal forebrain cholinergic pathway, and gliosis. Abeta1-42 plaques develop in specific brain regions, including hippocampus and cortex, as well as in the vasculature. Abeta1-42 might promote neurodegeneration through the induction of free radicals and disruption of Ca2+ homeostasis, giving rise to the symptoms of AD. Abeta1-42 interacts with the alpha7 subtype of the nicotinic acetylcholine receptor (alpha7 nAChR), which is widely expressed throughout the central and peripheral nervous systems, as well as in several nonneuronal loci, such as epithelial cells, lymphoid tissues, and peripheral blood lymphocytes. Western blot and autoradiographic analyses indicate that the alpha7 nAChR subunit protein is up-regulated in human brain samples from Alzheimer patients, as well as in animal models of AD (Dineley et al., 2001; Bednar et al., 2002), and might be involved in nicotine-mediated reduction of Abeta1-42 deposition (Hellstrom et al., 2004), although the nature of this relationship remains ill-defined. We have undertaken a semiquantitative histological evaluation of alpha7 nAChR expression in a mouse model of AD pathology, as well as a comparison of alpha7 nAChR levels in lymphocytes from AD patients and control subjects.
Jones
Ian W
IW
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK. bssiwj@bath.ac.uk
Westmacott
Adam
A
Chan
Elcie
E
Jones
Roy W
RW
Dineley
Kelly
K
O'Neill
Michael J
MJ
Wonnacott
Susan
S
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001344:Autopsy; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008214:Lymphocytes; D051379:Mice; D009154:Mutation; D011978:Receptors, Nicotinic / Q000235:genetics*; D012016:Reference Values; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor