Correlation of the clinical severity of Alzheimer's disease with an aberration in mitochondrial DNA (antDNA)

Controversy exists about which of the well-established neurobiological abnormalities in Alzheimer's disease (AD) relate directly to the clinical disabilities. Because of an interest in the mitochondrial lesion in AD, we tested the correlation between clinical disability (measured by the Clinical Dementia Rating [CDR] scale) and an anomaly in mitochondrial DNA (mtDNA) in AD brain. Simultaneous polymerase chain reaction (PCR) amplification of the CO1 gene in mtDNA and CO1 pseudogenes in nuclear DNA (nDNA) were performed in samples from AD and non-AD brain, and the ratios of mtDNA/nDNA amplicons calculated. This approach utilizes PCR amplification of endogenous nDNA as a normalization standard for the amplification of mtDNA. We examined total DNA from the brains of Caucasian residents of a Jewish nursing home (86 AD and 26 non-AD controls). These patients had been closely followed clinically until death and then autopsied. In this sample, the degree of cognitive impairment in the AD patients correlated with the reduction in the amplification of the mtDNA gene (rho = 0.23; p = 0.034), but not with the density of neuritic plaques (p = 0.109). These results agree with the suggestion that the well-documented impairment in brain-energy metabolism in AD may be a direct cause of the clinical disability.