Estrogen receptor α (ERα) may be implicated in the pathogenesis of Alzheimer’s disease (AD). The aim of this study was to clarify the association between ERα gene polymorphisms and AD-related pathologic changes. The staging of neurofibrillary tangles (NFT) and senile plaques (SP) was performed according to the method by Braak and Braak and two polymorphisms, <i>Pvu</i>II (P or p) and <i>Xba</i>I (X or x), of the ERα gene were typed in 551 Japanese cadavers (294 men and 257 women; mean age, 80.8 years). Distributions of the NFT and SP stages significantly correlated with age (NFT: r = 0.306, p < 0.0001; SP: r <i>=</i> 0.237, p < 0.0001) and were significantly higher in patients with the apolipoprotein E &#917;4 allele (p < 0.0001). Possession of the P allele showed a trend to be associated with a more serious NFT stage, but had no relationship with the SP stage. In men, a significant association between <i>Pvu</i>II polymorphism and the NFT stage (p = 0.002) was found, revealing a gene- dose effect of the P allele. Similar results were obtained in the men without the &#917;4 allele (p = 0.011). Multiple regression analyses demonstrated that age was the strongest determinant of the NFT stage, possession of the &#917;4 allele was the next strongest, and <i>Pvu</i>II polymorphism was the third strongest (p < 0.0001, R² = 0.144). The<i> Xba</i>I polymorphism did affect neither the NFT stage nor the SP stage. In conclusion, the <i>Pvu</i>II polymorphism of the ERα gene is associated with Braak NFT stages and possession of the P allele may act as a risk factor for AD in Japanese men, especially in those without the &#917;4 allele.