Table 1.
mtDNA alterations in AD.
| Alteration Type | Observed Change | Analysis Method | Patient Sample | References |
|---|---|---|---|---|
| mtDNA deletion | mtDNA Δ4977 | dilution-PCR | cortex, putamen, and cerebellum | [107] |
| mtDNA deletion | - | real-time PCR and long-extension PCR | putamen, frontal cortex, and substantia nigra | [222] |
| mtDNA deletion | ↑8-OHdG, ↑mtDNA fragmentation, ↓mtDNA | semiquantitative PCR analysis | temporal lobe tissue | [223] |
| mtDNA deletion | ↑8-OHdG and ↓mtDNAΔ4977 deletion | Kinetics PCR | frontal cortex | [110] |
| mtDNA deletion | ↓ mtDNA/ nDNA ratio | real-time PCR | hippocampus and cerebellum | [104] |
| mtDNA deletion | ↓ mtDNA copy number | Exome sequencing | brain tissue | [105] |
| mtDNA deletion | ↓ mtDNA copy number | real-time PCR | blood leukocytes | [224] |
| mtDNA mutation | Frequencies are not increased | RMC assay | brain tissue | [118] |
| mtDNA mutation | ↓mtDNA, ↑mutation frequencies (T→C/A→G and G→A/C→T transitions) |
ultra-sensitive next-generation sequencing |
hippocampus, middle temporal gyrus, and the visual and cerebellar cortex | [108] |
| mtDNA point mutation | T→C conversion | ultra-sensitive next-generation sequencing | hippocampus | [108] |
| mtDNA point mutation | m.7476C→T and m.15812 G→A | PCR sequencing | frontal and parietal associative cortex | [106] |
| mtDNA point mutation | tRNA (Asn) gene variant at nucleotide pair 5075 | PCR sequencing | brain tissue | [225] |
| mtDNA point mutation | tRNA (Asn) gene variant at nucleotide pair 3646 | D-loop sequencing | brain tissue | [226] |
| mtDNA methylation | D-loop↑ and MT-ND1 ↓ | PCR sequencing | entorhinal cortex | [227] |
| mtDNA methylation | D-loop methylation levels: MCI > control group > AD early stages > AD advanced stages | MS-HRM | peripheral blood | [228] |
Abbreviations: AD, Alzheimer’s disease; PCR, polymerase chain reaction; 8-OHdG, 8-oxo-7,8-dihydro-29-deoxyguanosine; RMC assay, a highly sensitive method that discriminates wild-type from mutated DNA based on the cleavage at a specific restriction site (TaqI) composed of all four canonical nucleotide (50 TCGA30); D-loop, displacement-loop; MT-ND1, a gene encoding for NADH-ubiquinone oxidoreductase chain 1, which is a core subunit of complex I; MCI, mild cognitive impairment; MS-HRM, methylation-sensitive high-resolution melting.