24-Hydroxycholesterol is a natural sterol, which serves as a positive allosteric modulator of N-Methyl-d-Aspartate (NMDA) receptorsR, and a potent activator of the transcription factors LXR. In Vitro: 24S-hydroxycholesterol oxysterol-generating enzyme Cyp46a1 is overexpressed during the angiogenic switch in rat insulin promoter 1-T-antigen 2 (RIP1-Tag2) pNET formation^[1]. In Vivo: Hypoxia inducible factor-1a (HIF-1α) controls the overexpression of the enzyme Cyp46a1, which generates the oxysterol 24-hydroxycholesterol in a pancreatic neuroendocrine tumor (pNET) model commonly used to study neoangiogenesis. The activation of the HIF-1α-24S-HC axis ultimately leads to the induction of the angiogenic switch through the positioning of proangiogenic neutrophils in proximity to Cyp46a1⁺ islets^[1]. 24-hydroxycholesterol levels are increased at 2-4 months in the untreated 5XFAD mouse brain and then became similar to those in the B6SJL mouse brain^[2].