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Attenuation of Aβ deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking
Author(s) -
Court J. A.,
Johnson M.,
Religa D.,
Keverne J.,
Kalaria R.,
Jaros E.,
McKeith I. G.,
Perry R.,
Naslund J.,
Perry E. K.
Publication year - 2005
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2005.00674.x
Subject(s) - nicotine , medicine , endocrinology , entorhinal cortex , hippocampus , nicotinic agonist , temporal cortex , pathology , receptor , physiology , biology , neuroscience
Investigating correlates of tobacco smoking provides the only currently available opportunity of examining effects of long‐term exposure of nicotinic receptors on a specific nicotinic agonist in human. Alzheimer‐type pathology (Aβ and abnormally phosphorylated tau assessed on the basis of AT8 immunoreactivity) together with vascular markers has been compared in age‐matched groups of normal elderly smokers and non‐smokers in the entorhinal cortex, an area of noted age‐related pathology. The density of total Aβ and diffuse Aβ immunoreactivity, together with formic acid‐extractable Aβ42 but not Aβ40, was reduced in smokers ( n = 10–18) compared with non‐smokers ( n = 10–20) ( P < 0.05). There was also a reduced percentage of cortical and leptomeningeal vessels with associated Aβ immunoreactivity in smokers ( n = 13) compared with non‐smokers ( n = 14) ( P < 0.005 and 0.05, respectively). There was a significant inverse correlation between formic acid‐extractable Aβ42 and pack years ( n = 34, r = −0.389, P = 0.025), with a similar trend for total Aβ immunoreactivity which did not reach statistical significance ( n = 30, r = −0.323, P = 0.082). In contrast, there were no significant group differences for vascular markers (collagen IV, α‐actin or glucose transporter 1), AT8 immunoreactivity or phosphate‐buffered saline‐soluble Aβ peptides, and no significant associations with gender for any of the measured parameters. These findings are consistent with previously reported reductions in histologically assessed amyloid plaques in aged human brain associated with tobacco use and dramatic lessening of Aβ deposits in APPsw mice after nicotine treatment. Development of nicotinic drugs to protect against β‐amyloidosis as one of the principal pathological hallmarks of brain ageing and Alzheimer's disease is indicated.