CLDN5 and early-onset autosomal dominant Alzheimer disease: For example, downregulation of CLDN5 in the brain allows for transfer of amyloid beta (Aβ), a primary indicator of Alzheimer’s disease (Jack et al., 2024), from the CNS into the periphery via the BBB; Aβ itself may autoregulate CLDN5 expression to allow for its clearance from the brain (Keaney et al., 2015).