Several non-mutually exclusive factors can produce conflicting results in association studies of common complex diseases, including genetic, clinical, and population heterogeneity.

A possible explanation for the inconsistency between results of different groups may be that the studied ACE I/D polymorphism may have no functional consequences but may be in linkage disequilibrium with a functional polymorphism linked to the AD risk. Further research is needed to elucidate any role that the ACE polymorphism may play in relation to sporadic and familial AD.

Regarding longevity, a recent observation (Kritchevsky et al., 2005) showed that older adults possessing the ID or DD genotype and who exercised achieved more benefit in preserving mobility function than did those with the II genotype. In our study, we confirm this data since 97 out of 111 (87.4%) of the analyzed centenarians carried the ID or DD genotype and did not show gross functional limitations (i.e., difficulty walking and climbing steps).

Centenarians showed the highest allele D frequency, although the value was not significant (0.694 versus 0.645 in controls, 0.663 in AD and 0.689 in FAD), thus suggesting that the D allele could belong to a set of epistatic alleles that have pleiotropic age-dependent effects.

The comparison between centenarians and controls had a power of 96.61%. However, recent studies on centenarians belonging to different ethnic groups (Choi et al., 2003; Panza et al., 2003) suggested that neither the ACE nor the APOE gene is significantly associated with longevity in the Korean population and in a population from Southern Italy, which did not confirm previous studies (Schachter et al., 1994).

In conclusion, our data do not suggest a possible involvement of the D allele in longevity; moreover, they do not support involvement of the ACE gene I/D polymorphism in sporadic and familial AD, nor do they support involvement of the APOE gene in longevity.

Acknowledgements

This study was supported by the Italian Ministry of Instruction, University and Research (grant nos. 2005051707-005 and 2005062887-004) and by the Cassa di Risparmio of Florence (grant no. 2003.1764).

References

APA (American Psychiatric Association), Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV). American Psychiatric Publishing, APA Press, Washington DC.

Choi, Y.H., Kim, J.H., Kim, D.K., Kim, J.W., Kim, D.K., Lee, M.S., Kim, C.H., Park, S.C. Distributions ACE and APOE polymorphisms and their relations with dementia status in Korean centenarians. J. A Biol. Sci. Med. Sci., Alzheimer's disease. Ital. J. Neurol. Sci., Elkins, J.S., Douglas, V.C., Johnston, S.C., Alzheimer disease risk and genetic variation in ACE: an analysis. Neurology, Hemming, M.L., Selkoe, D.J., Amyloid beta-protein is degraded by cellular angiotens