Manuel Mattheisen

Rare autosomal copy number variations in early-onset familial Alzheimer's disease

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • B V Hooli, Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA, USA.
  • ,
  • Z M Kovacs-Vajna
  • ,
  • K Mullin
  • ,
  • M A Blumenthal
  • ,
  • Manuel Mattheisen
  • C Zhang
  • ,
  • C Lange
  • ,
  • G Mohapatra
  • ,
  • L Bertram
  • ,
  • R E Tanzi
Over 200 rare and fully penetrant pathogenic mutations in amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) cause a subset of early-onset familial Alzheimer's disease (EO-FAD). Of these, 21 cases of EO-FAD families carrying unique APP locus duplications remain the only pathogenic copy number variations (CNVs) identified to date in Alzheimer's disease (AD). Using high-density DNA microarrays, we performed a comprehensive genome-wide analysis for the presence of rare CNVs in 261 EO-FAD and early/mixed-onset pedigrees. Our analysis revealed 10 novel private CNVs in 10 EO-FAD families overlapping a set of genes that includes: A2BP1, ABAT, CDH2, CRMP1, DMRT1, EPHA5, EPHA6, ERMP1, EVC, EVC2, FLJ35024 and VLDLR. In addition, CNVs encompassing two known frontotemporal dementia genes, CHMP2B and MAPT were found. To our knowledge, this is the first study reporting rare gene-rich CNVs in EO-FAD and early/mixed-onset AD that are likely to underlie pathogenicity in familial AD and perhaps related dementias.Molecular Psychiatry advance online publication, 11 June 2013; doi:10.1038/mp.2013.77.
Original languageEnglish
JournalMolecular Psychiatry
Publication statusPublished - 11 Jun 2013

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