Eine neue Studie hat herausgefunden, wie die APOE4-Genvariante den Energiehaushalt des Gehirns sabotiert, indem sie Neuronen daran hindert, Fett als Brennstoff zu verbrennen, wenn die Glukose zur Neige geht. Diese Entdeckung mithilfe von menschlichem Gehirngewebe und gentechnisch veränderten Mäusen könnte neue Wege zur Vorbeugung oder Verlangsamung der Alzheimer-Krankheit aufzeigen.

I’ve linked to the news release in the post above. In this comment, for those interested, here’s the link to the peer reviewed journal article:

https://www.nature.com/articles/s42255-025-01389-5

From the linked article:

Alzheimer’s discovery: How genetic variant disrupts brain’s energy supply

**A new study has pinpointed how the APOE4 gene variant sabotages the brain’s energy balance, blocking neurons from burning fat for fuel when glucose runs low, a discovery that could reveal new ways to prevent or slow Alzheimer’s disease.**

APOE4 was found to cause toxic lipid buildup. APOE normally helps shuttle cholesterol and other fats around the brain. APOE4, however, mismanages lipid transport, leading to fat accumulation inside neurons. This buildup stresses the neurons, making them more vulnerable to damage. The fat overload in astrocytes and microglia activates inflammatory pathways. Chronic brain inflammation contributes to neuronal death and worsens amyloid and tau pathology.

APOE4 also interfered with lysosomal function, the brain’s waste disposal mechanism. As a result, toxic proteins and damaged fats aren’t cleared effectively, which accelerates degeneration. Structural analysis showed that APOE4’s altered shape made it prone to sticking to cell membranes and lipids abnormally. This structural instability is the root of its malfunction.