Reactive microglia in aging and dementia: an immunohistochemical study of postmortem human brain tissue

Significantly increased up-regulation of HLA DR (major histocompatibility c omplex class II antigen) was seen using immunohistochemistry in postmortem brain tissue from demented patients with Alzheimer's disease (AD) (73 cases , 61 females/12 males, mean age 84 +/- 9 years) compared to controls (22 ca ses, 10 females/12 males, mean age 78 +/- 9 years). The counts of HLA DR-ex pressing activated microglia were significantly higher in female AD patient s compared to males, significantly higher in AD patients with the age at de ath greater than 75 years compared to those dying younger and higher, altho ugh not statistically significantly, in AD patients with the apolipoprotein E (ApoE) epsilon 4 allele compared to those patients not carrying this all ele. In contrast to the situation in AD patients, in the control cases the HLA DR expression was higher in males compared to females. Furthermore, in the very old non-demented patients (age at death > 80 years), a decrease in the up-regulation of HLA DR expression was observed. A significant correla tion between activated microglia and neurofibrillary tangles was seen in fe male AD patients compared to males, in AD cases without ApoE epsilon 4 alle le compared to those with this allele, in sporadic cases compared to famili al and in cases with senile rather than presenile onset of the disease. Our results indicate that there is an age- and/or sex-related variability in u p-regulation of HLA DR expression of microglia and that the linkage between this up-regulation and AD lesions is significantly influenced by the ApoE epsilon 4 allele, gender of subjects, age at onset and familiality of the d isease.