Vacuolar Protein-Sorting Proteins Are Reduced Even Before Cognitive Decline in a Mouse Model of Alzheimer's Disease

J Alzheimers Dis. 2023;96(3):1011-1017. doi: 10.3233/JAD-230686.

Abstract

Currently, interventions from the preclinical stage are considered necessary for the treatment of Alzheimer's disease (AD). Previous studies have reported that vacuolar protein-sorting protein (VPS), a retromer construct, is involved in the pathogenic mechanisms of AD and Parkinson's disease. This study evaluated VPS26, VPS29, and VPS35 before and after the onset of cognitive decline in an App knock-in mouse model of AD that more closely resembles the human pathology than previous AD models. The results showed that the expression of VPS26 and VPS35 decreased before the onset of cognitive decline, suggesting the possibility of anti-amyloid-β disease-modifying treatment targeting these proteins.

Keywords: Alzheimer’s disease; amyloid-β; retromer; vacuolar protein-sorting protein.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cognitive Dysfunction*
  • Humans
  • Mice
  • Protein Transport
  • Vesicular Transport Proteins / metabolism

Substances

  • Vesicular Transport Proteins
  • Amyloid beta-Peptides