Alzheimer’s disease (AD) is the most common form of dementia in adults, especially in people aged 65 years or over. AD is currently estimated to affect over 44 million people worldwide, with this number expected to double every 20 years. AD is therefore the most important contributor to cognitive decline and dementia globally. The main feature of AD is a progressive decline in cognitive function, including memory, thinking, language, and learning capacity. AD is associated with the deposition of amyloid beta protein, neuronal loss, synaptic dysfunction, neurofibrillary tangles, and brain atrophy in specific brain areas. AD is untreatable other than with medications used to manage symptoms. There is, consequently, a strong need for novel and effective agents for the treatment of AD.
Ageing is associated with oxidative stress, a contributory factor for onset and progression of AD. Oxidative DNA damage has been observed in the brains and peripheral blood lymphocytes of AD patients. The oxidative DNA damage in the brain cells can lead to neural dysfunction in patients with AD. Both nuclear and mitochondrial oxidative DNA damage are critical in the development of AD.
Notably, there is substantial evidence for dysregulated DNA repair in AD. Furthermore, a variant of OGG1
with reduced DNA repair activity is observed in AD patients and thus may promote increased DNA damage in those patients. A new treatment targeting oxidative mtDNA and the improvement in mitochondrial function, therefore, may provide a benefit to AD patients.