Alzheimer’s disease and the genetics of neuroprotection

As the world’s leading form of age-related dementia, Alzheimer’s disease (AD) is a devastating neurological disorder associated with severe emotional and economic burdens. Despite years of research, the underlying mechanism behind this disease remains unclear. The current prevailing theory relies on the deposition of toxic amyloid beta (Aβ), which promotes the formation of phosphorylated tau tangles, and together these damaging changes drive the loss of neurons. Much of AD development can be attributed to genetic influences, including pathogenic variants of β-amyloid precursor protein, presenilins 1 and 2, and the presence of apolipoprotein 4. However, there are other subtle, yet significant variations within our genome that contribute to protecting us against AD. Variants of the phospholipase Cγ2 and toll-like receptor 4 genes have been associated with reduced risk of developing AD, as well as increased longevity of patients. These neuroprotective variants can guide the development of future therapeutic interventions for AD, as current strategies have proven lackluster.