| First Author | Konings SC | Year | 2023 |
| Journal | Life Sci Alliance | Volume | 6 |
| Issue | 8 | PubMed ID | 37290814 |
| Mgi Jnum | J:348463 | Mgi Id | MGI:7489087 |
| Doi | 10.26508/lsa.202201887 | Citation | Konings SC, et al. (2023) Apolipoprotein E intersects with amyloid-beta within neurons. Life Sci Alliance 6(8) |
| abstractText | Apolipoprotein E4 (ApoE4) is the most important genetic risk factor for Alzheimer's disease (AD). Among the earliest changes in AD is endosomal enlargement in neurons, which was reported as enhanced in ApoE4 carriers. ApoE is thought to be internalized into endosomes of neurons, whereas beta-amyloid (Abeta) accumulates within neuronal endosomes early in AD. However, it remains unknown whether ApoE and Abeta intersect intracellularly. We show that internalized astrocytic ApoE localizes mostly to lysosomes in neuroblastoma cells and astrocytes, whereas in neurons, it preferentially localizes to endosomes-autophagosomes of neurites. In AD transgenic neurons, astrocyte-derived ApoE intersects intracellularly with amyloid precursor protein/Abeta. Moreover, ApoE4 increases the levels of endogenous and internalized Abeta(42) in neurons. Taken together, we demonstrate differential localization of ApoE in neurons, astrocytes, and neuron-like cells, and show that internalized ApoE intersects with amyloid precursor protein/Abeta in neurons, which may be of considerable relevance to AD. |
