Innovita Research Foundation

I.R.F. / Aging news / Diseases / 02080101

AD and Smoking
Posted on: August 1, 2002

Several investigations based on clinical epidemiology suggest that smoking might exert some protection from Alzheimer's disease. As nearly all people older than 65 years of age exhibit a few Alzheimer neurofibrillary tangles (NFT), or a few senile plaques (SP) or both, these changes can be meaningfully analyzed in the brain of any patient dying at an advanced age. Therefore, during this study, brains of all patients dying at the age of 65 years or older were collected and quantified NFT and SP according to a standardized protocol. Their smoking habits were inquired and related to the morphological data.

What could be concluded from experimental data? The difference in age at death between smokers and nonsmokers is known to be considerable, and this was also observed in our sample: smoking women on the average died 5 years earlier than nonsmoking women, smoking men 3 years earlier than nonsmoking men. To obtain reliable statistics age and sex-matched pairs comprising a smoker and a nonsmoker were selected. Comparing the individuals of these pairs, there was a slightly fewer SP and NFT (measured in area densities and in Braak stages) in smokers. Taking the entire sample, however, this difference was only statistically significant for the area density of SP. There were no statistically significant differences in the morphological parameters for the 44 age-matched pairs of male smokers/nonsmokers.

It is difficult to explain why smoking women should develop fewer Alzheimer-type changes than nonsmokers. This statistical finding that a certain group of patients develop fewer Alzheimer-type changes reflects the observation reported by van Duijn et al. who showed, with epidemiological data based on clinical observations, that smokers of a special group (families with Alzheimer's disease carrying the allele Apo E4) have a lower risk of developing Alzheimer's disease than nonsmokers. One particularly intriguing and apparently contradictory finding is that if smokers alone are considered, there is a positive correlation between the Alzheimer-type changes and the number of cigarettes consumed. This finding is particularly obvious for the NFT (Braak stages) but not for the SP.

Smokers had lower risk of developing Alzheimer's disease than nonsmokers, but could not show any dose dependency of this protective action. Considering some results, one can get the impression that smoking in women somehow affects the relationship between SP and NFT, which are normally numerically correlated. It is not possible to give a reasonable explanation of these contradictory results at the cellular level. It is not even certain whether the influence is exerted by nicotine itself or by some other substance within the cigarette smoke. If we assume that it is nicotine, the action could possibly be due to an effect on the nicotine receptors of acetylcholine, which are known to be dramatically lowered in Alzheimer's disease and to be increased under the influence of smoking. Recently, it was demonstrated that activation of cell surface receptors leads to an increase in the secretion of non-amylogenic proteolytic derivatives of the amyloid precursor protein. Although this was demonstrated in relation to the muscarinic acetylcholine receptor, one could imagine that the occupation of nicotine receptor sites might also provoke both the up-regulation of the receptors and an alteration of the cleavage of the amyloid precursor. In this way alterations of amyloid deposition in the SP could be stimulated. These, in turn, might influence the formation of NFT, which are known from statistical studies to be related to the SP. Such assumptions cannot be proven at the present time. Ending the story it could be concluded that Alzheimer-type changes in the brain tissue are influenced by smoking. Thus, also at the morphological level, smoking is an environmental influence on Alzheimer's disease.

Source: Acta Neuropathol (1997) 94 : 450-454
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