The best-known hallmarks of Alzheimer’s disease are clumps of misfolded amyloid-β (Aβ) and tau proteins, which aggregate in the brain. However, there is increasing awareness that Aβ and tau might not be the whole story — alterations in the blood–brain barrier (BBB) have also emerged as early markers of this neurodegenerative disorder1. The degree of disruption to the BBB correlates with the degree of cognitive dysfunction that a person experiences2, but what causes BBB breakdown has been unknown. Writing in Nature, Montagne et al.3 present evidence that the leading genetic risk factor for Alzheimer’s disease, apolipoprotein E4, is linked to BBB breakdown.ra
