The progressive neurodegenerative inflammatory age-related disease, Alzheimers disease (AD), is the most common cause of dementia in the elderly. Several factors, genetic and environmental, are involved in the onset of AD. Epidemiological data suggest that some genetic determinants of AD might reside in those polymorphisms for the immune system genes that regulate immune inflammatory responses, such as the Major Histocompatibility Complex (MHC). Therefore, MHC polymorphisms have been the focus of a large number of AD association studies. A possible association of HLA-A2 alleles with increased susceptibility to AD has been the subject of debate for more than 20 years, even if the results of these studies, in the various populations, are discordant. Thus, to gain insight in this matter, we have valuated if HLA-A2 allele is associated with AD in a homogeneous populations of Italian patients with sporadic AD. To this aim, we have analysed the distribution of HLA-A2 allele in patients with AD and controls, by PCR-SSP. Our results demonstrate a significant difference in the frequency of HLA-A2 allele between patients with AD and controls (46% vs. 38%). Then, our results confirm a positive role of HLA-A2 allele in the risk of onset of AD. Some of observed discrepancies may reflect the clinical or genetic heterogeneity of the populations studied or be due to methodological biases. Besides, if external agents such as viruses as suggested, play a role, these might be different in different population leading to different associations. However, in particular for discrepant results concerning HLA-A2, it has to be taken into account that there are many molecular HLA-A2 subtypes with different frequencies in different populations. So, further studies should include molecular typing of HLA-A2 subtypes.