Evaluating the role of pathogenic dementia variants in posterior cortical atrophy
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
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Elsevier
2016
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| Online Access: | https://eprints.nottingham.ac.uk/32271/ |
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| author | Carrasquillo, Minerva Barber, Imelda S. Lincoln, Sarah J. Murray, Melissa E. Camsari, Gamze Balci Khan, Qurat ul Ain Nguyen, Thuy Ma, Li Bisceglio, Gina D. Crook, Julia E. Younkin, Steven G. Dickson, Dennis W. Boeve, Bradley F. Graff-Radford, Neill R. Morgan, Kevin Ertekin-Taner, Nilüfer |
| author_facet | Carrasquillo, Minerva Barber, Imelda S. Lincoln, Sarah J. Murray, Melissa E. Camsari, Gamze Balci Khan, Qurat ul Ain Nguyen, Thuy Ma, Li Bisceglio, Gina D. Crook, Julia E. Younkin, Steven G. Dickson, Dennis W. Boeve, Bradley F. Graff-Radford, Neill R. Morgan, Kevin Ertekin-Taner, Nilüfer |
| author_sort | Carrasquillo, Minerva |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 ∼4300 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 ε4 association, and demonstrate the utility of NeuroX. |
| first_indexed | 2025-11-14T19:15:11Z |
| format | Article |
| id | nottingham-32271 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:15:11Z |
| publishDate | 2016 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-322712020-05-04T20:04:30Z https://eprints.nottingham.ac.uk/32271/ Evaluating the role of pathogenic dementia variants in posterior cortical atrophy Carrasquillo, Minerva Barber, Imelda S. Lincoln, Sarah J. Murray, Melissa E. Camsari, Gamze Balci Khan, Qurat ul Ain Nguyen, Thuy Ma, Li Bisceglio, Gina D. Crook, Julia E. Younkin, Steven G. Dickson, Dennis W. Boeve, Bradley F. Graff-Radford, Neill R. Morgan, Kevin Ertekin-Taner, Nilüfer 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 ∼4300 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 ε4 association, and demonstrate the utility of NeuroX. Elsevier 2016-01 Article PeerReviewed Carrasquillo, Minerva, Barber, Imelda S., Lincoln, Sarah J., Murray, Melissa E., Camsari, Gamze Balci, Khan, Qurat ul Ain, Nguyen, Thuy, Ma, Li, Bisceglio, Gina D., Crook, Julia E., Younkin, Steven G., Dickson, Dennis W., Boeve, Bradley F., Graff-Radford, Neill R., Morgan, Kevin and Ertekin-Taner, Nilüfer (2016) Evaluating the role of pathogenic dementia variants in posterior cortical atrophy. Neurobiology of Aging, 37 . pp. 38-44. ISSN 1558-1497 PCA poserior Alzheimer's disease dementia APOE TREM2 PSEN2 NeuroX http://www.sciencedirect.com/science/article/pii/S0197458015004807 doi:10.1016/j.neurobiolaging.2015.09.023 doi:10.1016/j.neurobiolaging.2015.09.023 |
| spellingShingle | PCA poserior Alzheimer's disease dementia APOE TREM2 PSEN2 NeuroX Carrasquillo, Minerva Barber, Imelda S. Lincoln, Sarah J. Murray, Melissa E. Camsari, Gamze Balci Khan, Qurat ul Ain Nguyen, Thuy Ma, Li Bisceglio, Gina D. Crook, Julia E. Younkin, Steven G. Dickson, Dennis W. Boeve, Bradley F. Graff-Radford, Neill R. Morgan, Kevin Ertekin-Taner, Nilüfer Evaluating the role of pathogenic dementia variants in posterior cortical atrophy |
| title | Evaluating the role of pathogenic dementia variants in posterior cortical atrophy |
| title_full | Evaluating the role of pathogenic dementia variants in posterior cortical atrophy |
| title_fullStr | Evaluating the role of pathogenic dementia variants in posterior cortical atrophy |
| title_full_unstemmed | Evaluating the role of pathogenic dementia variants in posterior cortical atrophy |
| title_short | Evaluating the role of pathogenic dementia variants in posterior cortical atrophy |
| title_sort | evaluating the role of pathogenic dementia variants in posterior cortical atrophy |
| topic | PCA poserior Alzheimer's disease dementia APOE TREM2 PSEN2 NeuroX |
| url | https://eprints.nottingham.ac.uk/32271/ https://eprints.nottingham.ac.uk/32271/ https://eprints.nottingham.ac.uk/32271/ |