This paradox pattern appears to continue into the preclinical AD stage as indicated by biomarkers, where lower BMI has been associated with higher levels of CSF p-tau 181 in midlife (Mathys et al., 2017), and later life obesity has been linked with lower levels of CSF p-tau (Zhang et al., 2022). Here, MAPT is linked to obesity due to melanocortin 4 receptor deficiency.