Phosphorylation-state dependent intraneuronal sorting of Aβ differentially impairs autophagy and the endo-lysosomal system

Autophagy. 2024 Jan;20(1):166-187. doi: 10.1080/15548627.2023.2252300. Epub 2023 Aug 29.

Abstract

AD: Alzheimer disease; APP: amyloid beta precursor protein; ATG: autophagy related; Aβ: amyloid-β; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; EEA1: early endosome antigen 1; FA: formic acid; GFP: green fluorescent protein; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAP2: microtubule-associated protein 2; nmAβ: non-modified amyloid-β; npAβ: non-phosphorylated amyloid-β; pAβ: phosphorylated amyloid-β; p-Ser26Aβ: amyloid-β phosphorylated at serine residue 26; p-Ser8Aβ: amyloid-β phosphorylated at serine residue 8; RAB: RAB, member RAS oncogene family; RFP: red fluorescent protein; SQSTM1/p62: sequestome 1; YFP: yellow fluorescent protein.

Keywords: Alzheimer’s disease; autophagic flux; neurodegeneration; phosphorylated Aβ; post-translationally modified Aβ; vesicular trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides* / metabolism
  • Autophagy* / physiology
  • Green Fluorescent Proteins / metabolism
  • Lysosomes / metabolism
  • Phosphorylation
  • Serine

Substances

  • Amyloid beta-Peptides
  • Green Fluorescent Proteins
  • Serine

Grants and funding

The work was supported by the Alzheimer Forschung Initiative e.V. [12854]; Alzheimer Forschung Initiative e.V. [17011]; Alzheimer Forschung Initiative e.V. [T1803]; Deutsche Forschungsgemeinschaft [WA1477/6-6]; Deutsche Forschungsgemeinschaft [WA1477/6-3].