Gliosis in relation to Alzheimer's hallmark lesions in aging and Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia among the elderly and accounts for 50-70% of all the demented cases. The major AD hallmark lesions are senile/neuritic plaques (SP/NP) and neurofibrillary tangles (NFT). The ApoE ε4 genotype is one of the riskfactors for AD. The present study showed that the prevalence of the ApoE ε4 genotype was higher among AD cases and the number of major AD hallmark lesions was higher in the AD subjects carrying this deleterious ApoE ε4 allele. The number of reactive astrocytes (RA) was significantly higher in AD subjects compared to nondemented ones. However, the number of activated microglia (AM) did not differ significantly between the demented and the non-demented group in this study. The ApoE genotype modified the positive correlation between the number of glial cells (RA and AM) and AD hallmark lesions. The correlation was stronger in AD subjects without the ApoE ε4 allele. When AD cases without NSAID treatment were studied, there were no significant differences in the amount of NFTs, RA or AM between different ApoE genotypes. The number of SP/NPs was only slightly higher in cases with the ApoE ε4. The number of RA correlated significantly with the βA load and the number of AM correlated significantly with the extent of NFT’s in AD cases without NSAID treatment. Regular NSAID treatment in AD subjects was associated with a significantly lower number of RA compared to the subjects without NSAID use. DNA-fragmentation was more pronounced in definite AD cases compared to probable AD. There was a significant correlation between DNA-fragmentation and NFT count in cases with the ApoE ε4 allele. The SP/NPs correlated with DNA-fragmentation in cases without the ApoE ε4 allele. The present study shows a complex association between the glia and AD lesions. This association seems to be modified by several risk factors e.g. the ApoE genotype. Epidemiological studies have proposed that NSAID treatment might be of benefit to an AD patient. Results obtained by this retrospective postmortem study support this notion. From the methodological point of view, however, it should be emphasized that a patient sample of 95 individuals is still rather small when analyzing pathological lesions influenced by several riskfactors and this influence being modified by the ApoE genotype. National Library of Medicine Classification: WL 359, QW 504.5 Medical subject headings: Alzheimer's disease; aging; gliosis; apolipoprotein E/ genetics; apoptosis; immunohistochemistry; human