Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old AppNL/NL Knock-In Mice

J Alzheimers Dis. 2018;66(2):801-809. doi: 10.3233/JAD-180410.

Abstract

Commonly used Alzheimer's disease mouse models are based on the ectopic overexpression of the human amyloid precursor protein (APP) gene, together with a mutant presenilin gene. Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (AppNL), failed to develop amyloid plaque aggregation or cognitive deficits. Here we characterized the effect of this mutation in more advanced ages. We show that 24-month-old AppNL/NL mice, despite presenting an age dependent increase in insoluble amyloid-β oligomers in the prefrontal cortex, they do not develop amyloid plaque deposition, reactive gliosis, or cognitive deficits.

Keywords: Aging; Alzheimer’s disease; amyloid plaques; behavior; cognition; knock-in.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Cognitive Dysfunction / etiology
  • Conditioning, Psychological
  • Cues
  • Disease Models, Animal
  • Exploratory Behavior
  • Fear
  • Gene Expression Regulation / genetics*
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics*
  • Prefrontal Cortex / metabolism*
  • Social Behavior

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor