Hypertension, diabetes, hyperlipidemia, and hyperhomocysteinemia collectively contribute to white matter lesions (WMLs) through abnormalities in the neurovascular unit (such as disruption of the blood–brain barrier, reduced cerebral blood flow, and microvascular disease) and the glymphatic system (such as the accumulation of metabolic waste and dysfunction of AQP4 water channels) [147,149,150]. This evidence concerns the gene AQP4 and hyperhomocysteinemia.