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

12 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
Externally publishedYes

Bibliographical note

Funding Information:
Support for this research was provided by the National Institutes of Health grants: National Institute on Aging (R01 AG032990 to Nilüfer Ertekin-Taner; U01 AG046139 to Nilüfer Ertekin-Taner and Steven G. Younkin; R01 AG018023 to Neill R. Graff-Radford and Steven G. Younkin; and AG025711, AG017216, AG003949 to Dennis W. Dickson); National Institutes on Neurologic Diseases and Stroke (R01 NS080820 to Nilüfer Ertekin-Taner), Mayo Alzheimer’s Disease Research Center: (P50 AG016574 to Dennis W. Dickson, Neill R. Graff-Radford, Steven G. Younkin, and Nilüfer Ertekin-Taner); Minerva M. Carrasquillo is supported in part by an MNIRGD Alzheimer’s Association grant. Imelda Barber is supported by a Joint Alzheimer’s Research UK and/or University of Nottingham Faculty of Medicine PhD studentship. The work in the KM laboratory is supported by funding from ARUK, and Kevin Morgan is a member of the Alzheimer’s Society Grant Advisory Board. The authors thank the patients and their families for their participation, without whom these studies would not have been possible.


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

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