... cortical neurons expressing APOE ε4, the strongest genetic risk factor for LOAD, have significantly diminished TRPML1-induced endolysosomal Ca 2+ release. Furthermore, we found that blocking TRPML1 function in primary neurons by depleting the TRPML1 agonist PI(3,5)P 2 via PIKfyve inhibition, recreated...

... dysfunction has been implicated in AD pathogenesis. We found, by examining cells stably expressing each APOE isoform, that APOE4 increases lysosomal trafficking, accumulates in enlarged lysosomes and late endosomes, alters autophagic flux and the abundance of autophagy proteins and lipid droplets, and alters...

... less infectious and of higher density, indicating defects in maturation. PLIN2 depletion also reduced protein levels and secretion of ApoE due to lysosomal degradation, but did not affect the density of ApoE-containing lipoproteins. However, ApoE overexpression in PLIN2-deficient cells did not restore...

...Thomas E. Willnow; Joachim Herz ABSTRACT The low density lipoprotein receptor-related protein (LRP) is a large multifunctional receptor implicated in the cellular uptake of functionally diverse ligands. Biochemical evidence suggests that LRP is a clearance receptor for apoE-rich remnant...