Untangle the mystery behind DS-associated AD - Is APP the main protagonist?

Ageing Res Rev. 2023 Jun:87:101930. doi: 10.1016/j.arr.2023.101930. Epub 2023 Apr 7.

Abstract

Amyloid precursor protein profusion in Trisomy 21, also called Down Syndrome (DS), is rooted in the genetic determination of Alzheimer's disease (AD). With the recent development in patient care, the life expectancy of DS patients has gradually increased, leading to the high prospect of AD development, consequently leading to the development of plaques of amyloid proteins and neurofibrillary tangles made of tau by the fourth decade of the patient leading to dementia. The altered gene expression resulted in cellular dysfunction due to impairment of autophagy, mitochondrial and lysosomal dysfunction, and copy number variation controlled by the additional genes in Trisomy 21. The cognitive impairment and mechanistic insights underlying DS-AD conditions have been reviewed in this article. Some recent findings regarding biomarkers and therapeutics of DS-AD conditions were highlighted in this review.

Keywords: APP; Alzheimer’s disease; Aβ plaques; Biomarkers; Down syndrome; Mitochondrial dysfunction; Tau phosphorylation; Theragnostic; Trisomy 21.

Publication types

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

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • DNA Copy Number Variations
  • Down Syndrome* / genetics
  • Down Syndrome* / metabolism
  • Humans
  • Neurofibrillary Tangles / metabolism
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Amyloid beta-Peptides
  • tau Proteins