Late-onset Alzheimer disease ge

Minerva M Carrasquillo, Qurat Ul Ain Khan, Melissa E Murray, Siddharth Krishnan, Jeremiah Aakre, V. Shane Pankratz, Thuy Nguyen, Li Ma, Gina Bisceglio, Ronald Carl Petersen, Steven G Younkin, Dennis W Dickson, Bradley F Boeve, Neill R Graff Radford, Nilufer Taner

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Abstract

Objective: To investigate association of genetic risk factors for late-onset Alzheimer disease (LOAD) with risk of posterior cortical atrophy (PCA), a syndrome of visual impairment with predominant Alzheimer disease (AD) pathology in posterior cortical regions, and with risk of "posterior AD" neuropathology. Methods: We assessed 81 participants with PCA diagnosed clinically and 54 with neuropathologic diagnosis of posterior AD vs 2,523 controls for association with 11 significant single nucleotide polymorphisms (SNPs) from published LOAD risk genome-wide association studies. Results: There was highly significant association with APOE ε4 and increased risk of PCA (p = 0.0003, odds ratio [OR] = 3.17) and posterior AD (p = 1.11 × 10 -17, OR = 6.43). No other locus was significant after corrections for multiple testing, although rs11136000 near CLU (p = 0.019, OR = 0.60) and rs744373 near BIN1 (p = 0.025, OR = 1. 63) associated nominally significantly with posterior AD, and rs3851179 at the PICALM locus had significant association with PCA (p = 0.0003, OR = 2.84). ABCA7 locus SNP rs3764650, which was also tested under the recessive model because of Hardy-Weinberg disequilibrium, also had nominally significant association with PCA risk. The direction of association at APOE, CLU, and BIN1 loci was the same for participants with PCA and posterior AD. The effects for all SNPs, except rs3851179, were consistent with those for LOAD risk. Conclusions: We identified a significant effect for APOE and nominate CLU, BIN1, and ABCA7 as additional risk loci for PCA and posterior AD. Our findings suggest that at least some of the genetic risk factors for LOAD are shared with these atypical conditions and provide effect-size estimates for their future genetic studies.

Original languageEnglish (US)
Pages (from-to)1455-1462
Number of pages8
JournalNeurology
Volume82
Issue number16
DOIs
StatePublished - Apr 22 2014

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Alzheimer Disease
Atrophy
Odds Ratio
Single Nucleotide Polymorphism
Onset
Alzheimer's Disease
Genome-Wide Association Study
Vision Disorders
Pathology
Locus

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Carrasquillo, M. M., Khan, Q. U. A., Murray, M. E., Krishnan, S., Aakre, J., Pankratz, V. S., ... Taner, N. (2014). Late-onset Alzheimer disease ge. Neurology, 82(16), 1455-1462. https://doi.org/10.1212/WNL.0000000000000335

Late-onset Alzheimer disease ge. / Carrasquillo, Minerva M; Khan, Qurat Ul Ain; Murray, Melissa E; Krishnan, Siddharth; Aakre, Jeremiah; Pankratz, V. Shane; Nguyen, Thuy; Ma, Li; Bisceglio, Gina; Petersen, Ronald Carl; Younkin, Steven G; Dickson, Dennis W; Boeve, Bradley F; Graff Radford, Neill R; Taner, Nilufer.

In: Neurology, Vol. 82, No. 16, 22.04.2014, p. 1455-1462.

Research output: Contribution to journalArticle

Carrasquillo MM, Khan QUA, Murray ME, Krishnan S, Aakre J, Pankratz VS et al. Late-onset Alzheimer disease ge. Neurology. 2014 Apr 22;82(16):1455-1462. https://doi.org/10.1212/WNL.0000000000000335
Carrasquillo, Minerva M ; Khan, Qurat Ul Ain ; Murray, Melissa E ; Krishnan, Siddharth ; Aakre, Jeremiah ; Pankratz, V. Shane ; Nguyen, Thuy ; Ma, Li ; Bisceglio, Gina ; Petersen, Ronald Carl ; Younkin, Steven G ; Dickson, Dennis W ; Boeve, Bradley F ; Graff Radford, Neill R ; Taner, Nilufer. / Late-onset Alzheimer disease ge. In: Neurology. 2014 ; Vol. 82, No. 16. pp. 1455-1462.
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AU - Khan, Qurat Ul Ain

AU - Murray, Melissa E

AU - Krishnan, Siddharth

AU - Aakre, Jeremiah

AU - Pankratz, V. Shane

AU - Nguyen, Thuy

AU - Ma, Li

AU - Bisceglio, Gina

AU - Petersen, Ronald Carl

AU - Younkin, Steven G

AU - Dickson, Dennis W

AU - Boeve, Bradley F

AU - Graff Radford, Neill R

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