NATURE: Alzheimer's dangerous gene APOE4 destroys blood-brain barrier

The contribution of blood vessels to dementia and Alzheimer's disease is increasingly recognizedRecent studies have shown that damage to the blood-brain barrier (BBB) is an early biomarker of cognitive impairment in humans, including early clinical stages of Alzheimer's diseasethe E4 variant oflipoprotein E (APOE4) is the main susceptibility to Alzheimer's disease, which can lead to accelerated decomposition of BBB and degeneration of cells around the cerebral capillaries, which maintain the integrity of BBBHowever, it is not clear whether the cerebrovascular effect of APOE4 causes cognitive dysfunctionrecently, researchers have found that, unlike individuals without APOE4 (?3/?3), there is damage to the BBB of individual hippocampuses and inner temporal lobes that carry APOE4 (?3/?4 or ?4/?4)This phenomenon is evident in carriers of APOE4 whose cognitive function is not impaired, and becomes more severe in carriers with cognitive impairment, and is not associated with amyloid-beta or tau lesionsin APOE4 carriers, high baseline levels of BBB endometera cell damage biomarkers in cerebrospinal fluid, soluble PDGFR beta, can predict future cognitive decline, even after controlling amyloid-beta and tau states, which is associated with increased activity in the cerebrospinal fluid BBB-degraded cyclic protein A-matrix metalloproteinase-9 pathway 19therefore, the results show that bBB damage is involved in APOE4-related cognitive decline and is independent of Alzheimer's pathology, which may be a potential therapeutic target for APOE4 carriers