Identification of Low Allele Frequency Mosaic Mutations in Alzheimer Disease

  • Carlo Sala FrigerioEmail author
  • Mark Fiers
  • Thierry Voet
  • Bart De StrooperEmail author
Part of the Neuromethods book series (NM, volume 131)


Germline mutations ofAPP,PSEN1, andPSEN2 genes cause autosomal dominant Alzheimer disease (AD). Somatic variants of the same genes may underlie pathogenesis in sporadic AD, which is the most prevalent form of the disease. Importantly, such somatic variants may be present at very low allelic frequency, confined to the brain, and are thus very difficult or impossible to detect in blood-derived DNA. Ever-refined methodologies to identify mutations present in a fraction of the DNA of the original tissue are rapidly transforming our understanding of DNA mutation and their role in complex pathologies such as tumors. These methods stand poised to test to what extend somatic variants may play a role in AD and other neurodegenerative diseases.

Key words

Single- cell sequencing Mosaicism Somatic variant Alzheimer’s disease Parkinson’s disease 


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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.VIB Center for Brain & Disease ResearchLeuvenBelgium
  2. 2.Center for Human GeneticsUniversitaire ziekenhuizen and LIND, KU LeuvenLeuvenBelgium
  3. 3.Department of Human GeneticsUniversity of Leuven, KU LeuvenLeuvenBelgium
  4. 4.Wellcome Trust Sanger InstituteHinxtonUK
  5. 5.Dementia Research Institute(UK-DRI)University College LondonLondonUK

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