{"doi":"10.1101/2020.04.07.20056614","title":"ADNC-RS, a clinical-genetic risk score, predicts Alzheimer’s pathology in autopsy-confirmed Parkinson’s Disease and Dementia with Lewy Bodies","abstract":"ABSTRACT Growing 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 defining 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. 208 consecutive autopsy-confirmed cases of PD or DLB 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 associate with risk for AD. In a training set of the first 127 individuals, we developed a logistic regression model predicting the presence of ADNC, using backward stepwise regression for model selection and 10-fold cross-validation to estimate performance. We then assessed model performance in a separate test set of the next 81 individuals. The best-fit model generated a risk score for ADNC (ADNC-RS) based on age at disease onset and genotype at three SNPs ( APOE, BIN1 , and SORL1 loci). In the training set, the area under the receiver operating curve (AUC) for this model was 0.751. In the test set, the AUC was 0.781. Individuals with ADNC-RS in the top quintile had four-fold likelihood of having AD pathology at autopsy compared with those in each of the lowest two quintiles. In patients with autopsy-confirmed PD or DLB a simple model incorporating three AD-risk SNPs and age at disease onset substantially enriches for concomitant AD pathology at autopsy, with implications for identifying LBD patients in which targeting amyloid-beta or tau is a therapeutic strategy.","journal":"medRxiv","year":2020,"id":126478,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":573957,"name":"Thomas F. Tropea","orcid":"0000-0003-0766-1496","position":1,"is_corresponding":false},{"id":227427,"name":"John Robinson","orcid":"0000-0001-6858-2367","position":2,"is_corresponding":false},{"id":80303,"name":"Eunran Suh","orcid":null,"position":3,"is_corresponding":false},{"id":574366,"name":"Howard I. Hurtig","orcid":null,"position":4,"is_corresponding":false},{"id":80309,"name":"Daniel Weintraub","orcid":"0000-0003-0633-7168","position":5,"is_corresponding":false},{"id":27603,"name":"Vivianna M. Van Deerlin","orcid":"0000-0002-7400-9097","position":6,"is_corresponding":false},{"id":107087,"name":"Edward B. Lee","orcid":"0000-0002-4589-1180","position":7,"is_corresponding":false},{"id":27606,"name":"John Q. Trojanowski","orcid":"0000-0002-9239-8794","position":8,"is_corresponding":false},{"id":76194,"name":"Alice S. Chen-Plotkin","orcid":"0000-0002-3387-2038","position":9,"is_corresponding":false},{"id":573956,"name":"David Dai","orcid":"0000-0001-8295-5561","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-18T23:15:23.509897Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}