Basic Science and Pathogenesis.

Background: Accumulation of oxidative DNA damage and its inefficient repair is a contributing factor to Alzheimer's disease (AD), yet the underlying mechanism remains largely unknown. Novel AD mouse models deficient for oxidative DNA damage repair were developed and characterized to better understand their impact on AD progression. In addition, vascularized cerebral organoids from AD patients were generated to translate findings to a human model of AD.

Age- and sex-dependent effects of DNA glycosylase Neil3 on amyloid pathology, adult neurogenesis, and memory in a mouse model of Alzheimer's disease.

Oxidative stress generating DNA damage has been shown to be a key characteristic in Alzheimer's disease (AD). However, how it affects the pathogenesis of AD is not yet fully understood. Neil3 is a DNA glycosylase initiating repair of oxidative DNA base lesions and with a distinct expression pattern in proliferating cells.