Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1

Ageing Res Rev. 2006 Nov;5(4):388-401. doi: 10.1016/j.arr.2005.11.001. Epub 2006 Jan 26.


Down syndrome (DS) is a genetically-based disorder which results in multiple conditions for sufferers. Amongst these is a common early incidence of Alzheimer's disease (AD) which usually affects DS individuals by their mid 40s. This fact provides a clue that one or more of the genes located on chromosome 21 may be involved in the onset of AD. Current evidence suggests that endosomal disorders may underlie the earliest pathology of AD, preceding the classical pathological markers of beta-amyloid plaque deposition and neurofibrillary tangles. Therefore, any genes involved in endocytosis and vesicle trafficking which are over-expressed in DS are novel candidates in the pathogenesis of AD. Intersectin-1 (ITSN1) and Down syndrome candidate region 1 (DSCR1) are two such genes. Extensive in vitro data and data from Drosophila indicates that the over-expression of either of these genes or their products results in inhibition or ablation of endocytosis in neuronal as well as non-neuronal cells. This review discusses in detail the known and potential roles of ITSN1 and DSCR1 in DS, AD, endocytosis and vesicle trafficking.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport / physiology*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Animals
  • DNA-Binding Proteins
  • Down Syndrome / pathology
  • Down Syndrome / physiopathology*
  • Endocytosis / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Muscle Proteins / physiology*


  • Adaptor Proteins, Vesicular Transport
  • DNA-Binding Proteins
  • ITSN1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • RCAN1 protein, human