Free-water imaging of the nucleus basalis of Meynert in apolipoprotein E4 carriers

The findings suggest that the <i>APOE</i> ε4/ε4 accelerates early microstructural alterations within the basal forebrain cholinergic system potentially through mechanisms involving altered lipid homeostasis, compromised neurovascular integrity, and sustained neuroinflammatory responses. These effects appear to indicate a genotype-specific vulnerability. Free-water imaging of the NBM emerges as a sensitive, non-invasive biomarker capable of detecting these <i>APOE</i>-modulated microstructural changes before overt atrophy or cognitive decline. Understanding the multifactorial pathways through which <i>APOE</i> ε4 and cardiovascular factors confer risk may enable increased understanding in genetically susceptible individuals prior to widespread neurodegeneration.