APOE ɛ4 exacerbates age-dependent deficits in cortical microstructure

Elijah Mak, Maria-Eleni Dounavi, Grégory Operto, Elina T Ziukelis, Peter Simon Jones, Audrey Low, Peter Swann, Coco Newton, Graciela Muniz Terrera, Paresh Malhotra, Ivan Koychev, Carles Falcon, Clare Mackay, Brian Lawlor, Lorina Naci, Katie Wells, Craig Ritchie, Karen Ritchie, Li Su, Juan Domingo Gispert, John T O’Brien.

Brain Communications (2024)

DOI: https://doi.org/10.1016/j.numecd.2023.07.020

Summary

The APOE ε4 gene is the strongest genetic risk factor for the most common form of Alzheimer’s disease, however, exactly how APOE4 contributes to Alzheimer’s is not fully clear. This was addressed in a collaboration between the PREVENT Dementia programme and the ALFA (ALzheimer’s and FAmilies) cohort in Barcelona.

Using an advanced brain imaging technique called Neurite Orientation Dispersion and Density Imaging (NODDI) in nearly 2,000 cognitively normal adults, the research teams found APOE4 worsened age-related loss of complexity of brain cell connections. These effects were most pronounced in areas of the brain vulnerable to Alzheimer’s disease and involved in memory function.

The findings, suggest APOE4 may promote the development of Alzheimer’s disease by hastening disruptive aging processes in neuron connectivity, especially in memory-critical areas.