Is the Point Mutation in Codon 331 of the Mitochondrial ND2 Gene Associated with Alzheimer’s Disease?

Abstract

Alzheimers disease (AD) is characterized by the presence of numerous neurofibrillary tangles and neuritic plaques in the neocortex, especially in the hippocampus. Besides there is ample evidence of disturbances of energy metabolism. Biochemical analyses demonstrated reduction of pyruvate dehydrogenase activity³ and abnormalities of the respiratory chain^4,5 in post mortem brain tissue from AD patients. Point mutations in mtDNA, as it was shown for some other encephalomyo-pathies and neurodegenerative disorders⁶ are reported in about 50% of AD patients.⁷ Two types of mutations, both at mtDNA position 5460 in codon 331 of the ND2 gene, are described (Figure 1): a G4A transition converting the wildtype amino acid alanine to threonine and a G4T mutation converting alanine to serine. None of the controls showed these mutations. Analyses of Petruzzella et al.² couldn’t confirm these findings, suggesting a neutral polymorphism not specifically related with AD. We report here the use of allele specific PCR to search for mutations at nt 5460 in post mortem brain and blood of AD patients and blood and muscle tissue of patients with presumed mitochondrial encephalomyopathies.