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

B. V. Hooli, Z. M. Kovacs-Vajna, K. Mullin, M. A. Blumenthal, M. Mattheisen, C. Zhang, C. Lange, G. Mohapatra, L. Bertram, R. E. Tanzi*

*Corresponding author for this work
35 Citations (Scopus)


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.

Original languageEnglish
JournalMolecular Psychiatry
Issue number6
Pages (from-to)676-681
Number of pages6
Publication statusPublished - 01.01.2014


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