{"doi":"10.1073/pnas.2220984120","title":"Guam ALS-PDC is a distinct double-prion disorder featuring both tau and Aβ prions","abstract":"The amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) of Guam is an endemic neurodegenerative disease that features widespread tau tangles, occasional α-synuclein Lewy bodies, and sparse β-amyloid (Aβ) plaques distributed in the central nervous system. Extensive studies of genetic or environmental factors have failed to identify a cause of ALS-PDC. Building on prior work describing the detection of tau and Aβ prions in Alzheimer's disease (AD) and Down syndrome brains, we investigated ALS-PDC brain samples for the presence of prions. We obtained postmortem frozen brain tissue from 26 donors from Guam with ALS-PDC or no neurological impairment and 71 non-Guamanian donors with AD or no neurological impairment. We employed cellular bioassays to detect the prion conformers of tau, α-synuclein, and Aβ proteins in brain extracts. In ALS-PDC brain samples, we detected high titers of tau and Aβ prions, but we did not detect α-synuclein prions in either cohort. The specific activity of tau and Aβ prions was increased in Guam ALS-PDC compared with sporadic AD. Applying partial least squares regression to all biochemical and prion infectivity measurements, we demonstrated that the ALS-PDC cohort has a unique molecular signature distinguishable from AD. Our findings argue that Guam ALS-PDC is a distinct double-prion disorder featuring both tau and Aβ prions.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":335200,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":5838,"name":"Jacob I. Ayers","orcid":"0000-0003-4544-2366","position":1,"is_corresponding":false},{"id":241309,"name":"Clifton L. Dalgard","orcid":"0000-0003-2025-8239","position":2,"is_corresponding":false},{"id":1064562,"name":"M. Madhy Garcia Garcia","orcid":"0000-0001-7053-0523","position":3,"is_corresponding":false},{"id":707751,"name":"Brianna M. Rivera","orcid":"0000-0003-4620-8483","position":4,"is_corresponding":false},{"id":32591,"name":"William W. Seeley","orcid":"0000-0003-1410-2027","position":5,"is_corresponding":false},{"id":323142,"name":"Daniel P. Perl","orcid":"0000-0002-4869-924X","position":6,"is_corresponding":false},{"id":5842,"name":"Stanley B. Prusiner","orcid":"0000-0003-1955-5498","position":7,"is_corresponding":false},{"id":401479,"name":"Carlo Condello","orcid":"0000-0002-8454-5360","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T01:09:58.338267Z","pmid":"36952379","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":[]}