Evaluating pathogenic dementia variants in posterior cortical atrophy

Minerva M. Carrasquillo, Imelda Barber, Sarah J. Lincoln, Melissa E. Murray, Gamze Balci Camsari, Qurat ul Ain Khan, Thuy Nguyen, Li Ma, Gina D. Bisceglio, Julia E. Crook, Steven G. Younkin, Dennis W. Dickson, Bradley F. Boeve, Neill R. Graff-Radford, Kevin Morgan, Nilüfer Ertekin-Taner

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to "posterior Alzheimer's disease (AD)" pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against w4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE e4 association, and demonstrate the utility of NeuroX.

Original languageEnglish (US)
Pages (from-to)38-44
Number of pages7
JournalNeurobiology of aging
StatePublished - 2016


  • APOE
  • Dementia
  • NeuroX
  • PCA
  • PSEN2
  • Posterior Alzheimer's disease
  • TREM2

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


Dive into the research topics of 'Evaluating pathogenic dementia variants in posterior cortical atrophy'. Together they form a unique fingerprint.

Cite this