Alzheimer’s Disease (AD) is the most common form of dementia in the elderly in which an interplay between genes and the environment is supposed to be involved. Mutations in Mitochondrial DNA (mtDNA) have been suspected to be causally related since Mitochondrial DNA is maternally inherited in a non-Mendelian way. All Mitochondrial tRNA genes of 24 AD patients and 50 healthy controls were investigated by sequencing method. Fifteen variations were found in different Mitochondrial tRNA genes. Eleven variations were polymorphic mutations. Four variations {C1631A, T1633A (tRNA Val), T14704C and T14723C (tRNA Glu)} filled the criteria for pathogenicity of mutation because of their: a) heteroplasmic state, b) conserved nucleotide, c) absence in the literature and d) absence in healthy controls. A12308G polymorphic mutation (tRNA Leu (CUN)) was found in 8 patients. This mutation has been reported in different neurodegenerative diseases as well as controls. We believe that these variations may have pathogenic effects in AD or have secondary effects in the disease process. The percentage of hetroplasmy may play a role in signs/symptoms or onset age of the disease.

Mitochondria contain their own DNA (mtDNA), which codes for 13 proteins (all subunits of the respiratory chain complexes), 22 tRNAs and 2 rRNAs. Several mtDNA point mutations as well as deletions have been shown to be causative in well-defined Mitochondrial disorders. A mixture of mutated and wild type mtDNA (heteroplasmy) is found in most of these disorders. Inheritance of mtDNA is maternal, and mothers with heteroplasmic mtDNA transmit different proportions of normal and mutated mtDNA to the children. Mitochondrial tRNA genes have a central role in Mitochondrial gene expression at the level of transcription, RNA processing and protein synthesis and they appear to be the Mitochondrial genes most frequently affected by mutations causing diseases in man.