APPARENT MTDNA HETEROPLASMY IN ALZHEIMERS-DISEASE PATIENTS AND IN NORMALS DUE TO PCR AMPLIFICATION OF NUCLEUS-EMBEDDED MTDNA PSEUDOGENES

In an unprecedented finding, Davis et al. [Davis, R. E., Miller, S., H errnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Th al, L. J., Beal, M. F., Howell, N. & Parker, W. D., Jr, (1997) Proc. N atl. Acad. Sci. USA 94, 4526-4531] used an unusual DNA isolation metho d to show that healthy adults harbor a specific population of mutated mitochondrial cytochrome c oxidase (COX) genes that coexist with norma l mtDNAs. They reported that this heteroplasmic population was present at a level of 10-15% in the blood of normal individuals and at a sign ificantly higher level (20-30%) in patients with sporadic Alzheimer's disease. We provide compelling evidence that the DNA isolation method employed resulted in the coamplification of authentic mtDNA-encoded CO X genes together with highly similar COX-like sequences embedded in nu clear DNA (''mtDNA pseudogenes''). We conclude that the observed heter oplasmy is an artifact.