Genetics, transcriptomics, and proteomics of Alzheimer's disease

J Clin Psychiatry. 2006 Apr;67(4):652-70. doi: 10.4088/jcp.v67n0418.

Abstract

Objective: To provide an updated overview of the methods used in genetic, transcriptomic, and proteomic studies in Alzheimer's disease and to demonstrate the importance of those methods for the improvement of the current diagnostic and therapeutic possibilities.

Data sources: MEDLINE-based search of 233 peer-reviewed articles published between 1975 and 2006.

Data synthesis: Alzheimer's disease is a genetically heterogeneous disorder. Rare mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes have shown the importance of the amyloid metabolism for its development. In addition, converging evidence from population-based genetic studies, gene expression studies, and protein profile studies in the brain and in the cerebrospinal fluid suggest the existence of several pathogenetic pathways such as amyloid precursor protein processing, beta-amyloid degradation, tau phosphorylation, proteolysis, protein misfolding, neuroinflammation, oxidative stress, and lipid metabolism.

Conclusions: The development of high-throughput genotyping methods and of elaborated statistical analyses will contribute to the identification of genetic risk profiles related to the development and course of this devastating disease. The integration of knowledge derived from genetic, transcriptomic, and proteomic studies will greatly advance our understanding of the causes of Alzheimer's disease, improve our capability of establishing an early diagnosis, help define disease subgroups, and ultimately help to pave the road toward improved and tailored treatments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / genetics
  • Brain Chemistry / genetics
  • Gene Expression Profiling
  • Genotype
  • Humans
  • Membrane Proteins / genetics
  • Mutation
  • Neurofibrillary Tangles / genetics
  • Oligonucleotide Array Sequence Analysis
  • Presenilin-1
  • Presenilin-2
  • Proteomics*
  • Research
  • Transcription, Genetic*

Substances

  • Amyloid beta-Peptides
  • Membrane Proteins
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2