To the best of our knowledge, this is the first study to demonstrate that brain myelin sulfatide deficiency, an early and highly specific AD metabolic abnormality driven by ApoE and accelerated by Aβ accumulation and many other factors, is sufficient to induce AD-like neuroinflammation characterized by strong activation of DAAs and DAMs, cognitive decline, and astroglial ApoE upregulation (Fig. 9). This evidence concerns the gene APOE and Mental deterioration.