Genetics of Posterior Cortical Atrophy
This study investigated the association of genetic risk factors for late-onset Alzheimer's disease (LOAD) with risk of posterior cortical atrophy (PCA). PCA is a syndrome of visual impairment with predominant Alzheimer's disease (AD) pathology in posterior cortical regions with risk of posterior AD neuropathology.
Our laboratory assessed participants with PCA diagnosed clinically (antemortem) or with neuropathologic diagnosis of posterior AD (postmortem neuropathological diagnosis of PCA), versus controls for association with single nucleotide polymorphisms (SNPs) from published LOAD risk genome-wide association studies.
The lab identified a significant effect for APOE and nominated CLU, BIN1 and ABCA7 as additional risk loci for PCA and posterior AD. These 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.
Our laboratory is currently analyzing the effect on PCA and posterior AD of variants at additional AD risk loci identified by large-scale LOAD genome-wide association studies.
- Carrasquillo MM, ul Ain Khan Q, Murray ME, Krishnan S, Aakre J, Pankratz V, Nguyen T, Li M, Bisceglio G, Petersen RC, Younkin SG, Dickson DW, Boeve BF, Graff-Radford NR, Ertekin-Taner N. Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD. Neurology. 2014;82:1455.
- Carrasquillo MM, Crook JE, Pedraza O, Thomas CS, Pankratz VS, Allen M, Nguyen T, Malphrus K, Li M, Bisceglio G, Roberts RO, Lucas JA, Smith GE, Ivnik RJ, Machulda MM, Graff-Radford NR, Petersen RC, Younkin SG, Ertekin-Taner N. Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease. Neurobiology of Aging. 2015;36:60.