Next Generation Sequencing in Alzheimer's Disease

Methods Mol Biol. 2016;1303:281-97. doi: 10.1007/978-1-4939-2627-5_17.


For the first time in the history of human genetics research, it is now both technically feasible and economically affordable to screen individual genomes for novel disease-causing mutations at base-pair resolution using "next-generation sequencing" (NGS). One popular aim in many of today's NGS studies is genome resequencing (in part or whole) to identify DNA variants potentially accounting for the "missing heritability" problem observed in many genetically complex traits. Thus far, only relatively few projects have applied these powerful new technologies to search for novel Alzheimer's disease (AD) related sequence variants. In this review, I summarize the findings from the first NGS-based resequencing studies in AD and discuss their potential implications and limitations. Notable recent discoveries using NGS include the identification of rare susceptibility modifying alleles in APP, TREM2, and PLD3. Several other large-scale NGS projects are currently underway so that additional discoveries can be expected over the coming years.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Animals
  • Cell Line, Tumor
  • Exome / genetics
  • Genetic Predisposition to Disease
  • Genomics
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Mice
  • Sequence Analysis, DNA