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 β-amyloid (Aβ) accumulates within neuronal endosomes early in AD. However, it remains unknown whether ApoE and Aβ 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/Aβ. Moreover, ApoE4 increases the levels of endogenous and internalized Aβ 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/Aβ in neurons, which may be of considerable relevance to AD.

Original languageEnglish
Article numbere202201887
JournalLife Science Alliance
Issue number8
Publication statusPublished - 2023 Aug

Subject classification (UKÄ)

  • Neurosciences

Free keywords

  • Humans
  • Amyloid beta-Protein Precursor/genetics
  • Apolipoprotein E4/genetics
  • Apolipoproteins E/genetics
  • Amyloid beta-Peptides/genetics
  • Alzheimer Disease/genetics
  • Neurons/physiology


Dive into the research topics of 'Apolipoprotein E intersects with amyloid-β within neurons'. Together they form a unique fingerprint.

Cite this