To explore the mutations in mitochondrial DNA (mtDNA) and the risk of developing early-onset Alzheimer′s disease(AD).

From March 2014 to April 2020, four pedigrees with maternal inherited characteristics of AD were recruited from the collected pedigree samples of early-onset familial AD. The entire mtDNA sequence was sequenced and compared with the modified Cambridge reference sequence. The latest version of mtDNA classification system database was used to classify mitochondrial haplotypes. Variation analysis method: the phylogenetic tree was used to find out the branch end private variation sites of each family sample proband, the MitoTool was used to analyze the conservatism of variation, and the PhyloTree was used to check whether these mutations were the identification variation of other haplotype groups. The pathogenicity of these variants was predicted by literature and database search, and SIFT pathogenicity prediction (2015). I-TASSER was used to predict the protein structure and Pymol was used to visualize the protein structure homology and to simulate the tertiary protein structure for analysis of the protein structural change.

A rare and non-synonymous variation m.8978T>C was detected. The conservative coefficient of this site was 1.0, and the pathogenicity score was high. The tertiary structure of MT-ATP6 protein was simulated by homology analysis, which showed the structural changes of the branched chain residues.

Mutation m.8978T>C of mtDNA may have potential pathogenicity and affect the onset of AD through the decline of mitochondrial function.

Alzheimer disease; Mitochondria; DNA; Mutation