Genetic breakthrough suggests APOE variants drive most Alzheimer's cases

A comprehensive review of more than 450,000 participants finds the APOE gene’s E3 and E4 variants together may account for an estimated 72–93% of Alzheimer’s cases, and that about 45% of all dementia cases link to APOE.

Researchers report that the APOE gene may account for a very large share of Alzheimer’s disease cases. The finding comes from a comprehensive review of studies that together involved more than 450,000 participants. The authors emphasise the roles of the common E3 variant alongside the better-known E4 variant. They say targeting APOE or the pathways it affects could point to new gene-based or drug treatments, though they present this as a research direction rather than an established therapy. Key findings: - The review pooled evidence from multiple studies covering over 450,000 people and focused on how APOE variants influence Alzheimer’s, dementia, and early brain changes. - Researchers report that the E3 and E4 variants of APOE together may account for roughly 72–93% of Alzheimer’s cases. - Overall, the analysis linked about 45% of all dementia cases to APOE. - People with two copies of E4 were at highest risk and tended to develop disease earlier, while two copies of E2 were associated with lower risk. - The authors and independent experts note that lifestyle and environmental factors (such as smoking, poor cardiovascular health and social isolation) also influence dementia risk, and that routine genotype testing is not currently available through the NHS. Summary: The study suggests APOE has a larger role in Alzheimer’s than previously estimated and highlights APOE and its molecular pathways as priorities for further research, including possible gene-targeting approaches. Independent specialists welcomed the work but urged caution about interpreting susceptibility as direct causation and stressed the need for clinical trials that focus on higher-risk groups to determine whether interventions can change outcomes.