Proceedings of the National Academy of Sciences · 2017 · 157 citations · 80 references
Life SciencesNeurologyNeuroscienceDementiaMolecular NeurobiologyMolecular NeuroscienceAlzheimer DiseaseAmyloid FormationNeurodegenerative DiseasesNeurodegenerative DisordersProtein AggregationProtein Aggregation DisordersAmyloid Beta AggregationAmyloid Beta PeptidesAmyloid ClearanceAmyloid PlaquesAmyloid ToxicityBlood - Brain Barrier TransportBlood-brain Barrier Peptide TransportCerebral Vessels
Significance Deposition of amyloid-β (Aβ) peptide in the form of parenchymal plaques and Aβ accumulation in the walls of cerebral vessels as cerebral amyloid angiopathy (CAA) are pathological hallmarks of Alzheimer’s disease (AD). The clusterin ( CLU ) gene, which confers AD risk, is associated with amyloid deposition. Here we show that loss of CLU promotes cerebrovascular CAA, yet significantly reduces the amount of parenchymal plaques by altering perivascular drainage of Aβ in the APP/PS1 mouse model of AD. The absence of CLU in these mice is associated with a lower number of hemorrhages and a decrease in inflammation. These results suggest that CLU functions as a major Aβ chaperone to maintain Aβ solubility along interstitial fluid drainage pathways and prevent CAA formation.
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Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Karen Hsiao, Paul F. Chapman, Steven P. Nilsen et al. · Science · 1996 · 4.2K citations