Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from elderly patients with Alzheimer's disease

To determine whether pathogenic mutations in mtDNA are involved in phenotyp ic expression of Alzheimer's disease (AD), the transfer of mtDNA from elder ly patients with AD into mtDNA-less (rho(0)) HeLa cells was carried out by fusion of platelets or synaptosomal fractions of autopsied brain tissues wi th rho(0) HeLa cells. The results showed that mtDNA in postmortem brain tis sue survives for a long time without degradation and could be rescued in rh o(0) HeLa cells. Next, the cybrid clones repopulated with exogenously impor ted mtDNA from patients with AD were used for examination of respiratory en zyme activity and transfer of mtDNA with the pathogenic mutations that indu ce mitochondrial dysfunction. The presence of the mutated mtDNA was restric ted to brain tissues and their cybrid clones that formed with synaptosomes as mtDNA donors, whereas no cybrid clones that isolated with platelets as m tDNA donors had detectable mutated mtDNA, However, biochemical analyses sho wed that all cybrid clones with mtDNA imported from platelets or brain tiss ues of patients with AD restored mitochondrial respiration activity to almo st the same levels as those of cybrid clones with mtDNA from age-matched no rmal controls, suggesting functional integrity of mtDNA in both platelets a nd brain tissues of elderly patients with AD. These observations warrant th e reassessment of the conventional concept that the accumulation of pathoge nic mutations in mtDNA throughout the aging process is responsible for the decrease of mitochondrial respiration capacity with age and with the develo pment of age-associated neurodegenerative diseases.