Beta-amyloidosis in normal aging and transmitter signaling in human temporal lobe.
Interactions between abnormal amyloid precursor protein metabolism and cholinergic dysfunction are increasingly apparent. Both of these major features of Alzheimer's disease occur in restricted loci in normal aging--a potential model for early Alzheimer type pathology. Entorhinal cortex is particularly vulnerable to beta-amyloidosis and compared with other cortical areas is remarkable for the relatively high density of nicotinic (3H-nicotine) but not other cholinergic or glutamate receptor binding. With increasing age, post-maturity, there is a persistent decline in nicotinic receptor binding in entorhinal cortex whereas muscarinic M1 and non-M1, glutamate NMDA and non-NMDA receptors are spared. Normal elderly individuals, distinguished by the absence of beta A4 immunoreactive plaques in this area, are differentiated from those with plaques by higher nicotine binding. Amongst individuals with an established history of smoking tobacco, nicotinic receptor binding and hippocampal choline acetyltransferase were elevated compared with non-smokers and preliminary evidence indicates a reduced density of cortical plaques. These findings are consistent with the hypothesis that down regulation of the nicotinic cholinergic receptor--a ligand gated calcium channel known to control the expression of neurotrophins--plays a role in the evolution of Alzheimer-type pathology.
Perry
E K
EK
Medical Research Council Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom.
Court
J A
JA
Lloyd
S
S
Johnson
M
M
Griffiths
M H
MH
Spurden
D
D
Piggott
M A
MA
Turner
J
J
Perry
R H
RH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides; D000686:Amyloidosis / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D005333:Fetus; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000502:physiology*; D012016:Reference Values; D015398:Signal Transduction; D013702:Temporal Lobe / Q000503:physiopathology*
D016229:Amyloid beta-Peptides; D018377:Neurotransmitter Agents