MITOCHONDRIAL-DNA SEQUENCE-ANALYSIS OF 4 ALZHEIMERS-DISEASE AND PARKINSONS-DISEASE PATIENTS

The mitochondrial DNA (mtDNA) sequence was determined on 3 patients wi th Alzheimer's disease (AD) exhibiting AD plus Parkinson's disease (PD ) neuropathologic changes and one patient with PD. Patient mtDNA seque nces were compared to the standard Cambridge sequence to identify base changes. In the first AD + PD patient, 2 of the 15 nucleotide substit utions may contribute to the neuropathology, a nucleotide pair (np) 43 36 transition in the tRNA(Gln) gene found 7.4 times more frequently in patients than in controls, and a unique np 721 transition in the 12S rRNA gene which was not found in 70 other patients or 905 controls, In the second AD + PD patient, 27 nucleotide substitutions were detected , including an np 3397 transition in the ND1 gene which converts a con served methionine to a valine. In the third AD + PD patient, 2 polymor phic base substitutions frequently found at increased frequency in Leb er's hereditary optic neuropathy patients were observed, an np 4216 tr ansition in ND1 and an np 13708 transition in the ND5 gene, For the PD patient, 2 novel variants were observed among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an np 15851 missense mutation in the cytb gene. Further studies will be required to demonst rate a causal role for these base substitutions in neurodegenerative d isease. (C) 1996 Wiley-Liss, Inc.