The Role of Unmethylated 5′-C-Phosphate-G-3′ (CpG) Motifs in Mitochondrial and Bacterial DNA in the Pathogenesis of Alzheimer’s Disease

Alzheimer’s disease (AD) is a leading form of dementia, marked by complex neuropathological features such as amyloid-β (Aβ) plaques and tau tangles. Recent research highlights the significant role of unmethylated cytosine–phosphate–guanine (CpG) motifs, short DNA sequences where a cytosine nucleotide is directly followed by a guanine nucleotide, linked by a phosphate group, in the disease’s development. CpG motifs, predominantly found in bacterial and mitochondrial DNA, can provoke immune responses when they appear in unexpected contexts. This review explores the intricate relationship between unmethylated CpG DNA and AD pathogenesis, investigating the mechanisms by which bacterial DNA enters the brain, activates immune pathways, and contributes to the progression of Alzheimer’s disease. Understanding these processes may offer new avenues for research and therapeutic intervention in AD.