The Role of the Rare Variants in the Genes Encoding the Alpha-Ketoglutarate Dehydrogenase in Alzheimer’s Disease

There is increasing evidence that several mitochondrial abnormalities are present in the brains of patients with Alzheimer’s disease (AD). Decreased alpha-ketoglutarate dehydrogenase complex (?KGDHc) activity was identified some AD. The ?KGDHc a key enzyme Krebs cycle. This very sensitive to harmful effect reactive oxygen species, which gives them critical role Alzheimer and research area. Previously, genetic risk factors were described association Our aim analyze associations rare damaging variants genes encoding subunits three (OGDH, DLST, DLD) sequenced from different brain regions 11 histologically confirmed AD blood further 35 patients. As control group, we screened 134 persons whole-exome sequencing. In all subunits, one–one variant unknown significance based on American College Medical Genetics Genomics (ACMG) classification. Based literature our experience, R263H mutation DLD gene seems likely be pathogenic. cerebral areas, mutational profile same, indicating presence germline variants. We hypothesize heterozygous missense may have as mild factor.