ADNC-RS, a clinical-genetic risk score, predicts Alzheimer ’s pathology in autopsy-confirmed Parkinson’s disease and Dementia with Lewy bodies

AbstractGrowing evidence suggests overlap between Alzheimer ’s disease (AD) and Parkinson’s disease (PD) pathophysiology in a subset of patients. Indeed, 50–80% of autopsy cases with a primary clinicopathological diagnosis of Lewy body disease (LBD)—most commonly manifesting during life as PD—have concomitant amyloid-beta and tau pathology, the def ining pathologies of AD. Here we evaluated common genetic variants in genome-wide association with AD as predictors of concomitant AD pathology in the brains of people with a primary clinicopathological diagnosis of PD or Dementia with Lewy Bodies (DLB), diseases both characterized by neuronal Lewy bodies. In the first stage of our study, 127 consecutive autopsy-confirmed cases of PD or DLB from a single center were assessed for AD neuropathological change (ADNC), and these same cases were genotyped at 20 single nucleotide polymorphisms (SNPs) found by genome-wide association study to associat e with risk for AD. In these 127 training set individuals, we developed a logistic regression model predicting the presence of ADNC, using backward stepwise regression for model selection and tenfold cross-validation to estimate performance. The best-fit model generated a risk score for ADNC (ADNC-R S) based on age at disease onset and genotype at three SNPs (APOE,BIN1, andSORL1 loci), with an area under the receiver operating curve (AUC) of 0.751 in our training set. In the replication stage of our study, we assessed model performa...
Source: Acta Neuropathologica - Category: Neurology Source Type: research