Dangerous leaks: blood-brain barrier woes in the aging hippocampus

Abstract

A leaky blood-brain barrier has long been implicated in cognitive dysfunction in aging and neurodegeneration, but reliable human data were lacking. Here, Montagne et al. (2015) provide the first in vivo evidence of blood-brain barrier disruption in the aging hippocampus and in minimal cognitive impairment.

Figure 1. Hypothetical Mechanisms by which Aβ May Induce BBB Alterations and Hippocampal Dysfunction

Aβ damages pericytes leading to suppression of mfsd2a expression in endothelial cells and increased endothelial vesicular transport. Aβ also causes endothelial Ca²⁺ overload through activation of TRPM2 channels, which contributes to the BBB disruption. Vascular damage reduces Aβ clearance and promotes tau phosphorylation. The alteration in homeostasis caused by the BBB disruption, in concert with the deleterious effects of Aβ and tau on synaptic function, may result in hippocampal dysfunction and cognitive deficits.