Mitochondrial damage in Alzheimer's disease varies with apolipoprotein E genotype

Brain metabolism and the activity of the alpha -ketoglutarate dehydrogenase complex (KGDHC), a mitochondrial enzyme, are diminished in brains from pat ients with Alzheimer's disease (AD). In 109 subjects, the Clinical Dementia Rating (CDR) score was highly correlated with brain KGDHC activity. In AD patients who carried the epsilon 4 allele of the apolipoprotein E gene (Apo E4), the CDR score correlated better with KGDHC activity than with the dens ities of neuritic plaques or neuritic tangles. In contrast, in patients wit hout ApoE4, the CDR score correlated significantly better with tangles and plaques than with KGDHC activity. The results suggest that mitochondrial/ox idative damage may be more important for the cognitive dysfunction in AD pa tients who early ApoE4 than in those who do not.