{"doi":"10.1002/alz.14225","title":"Associations between misfolded alpha‐synuclein aggregates and Alzheimer's disease pathology in vivo","abstract":"INTRODUCTION: We examined the relations of misfolded alpha synuclein (α-synuclein) with Alzheimer's disease (AD) biomarkers in two large independent cohorts. METHODS: We included Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably Two (BioFINDER-2) and Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (n = 2315, cognitively unimpaired, mild cognitive impairment, AD dementia) who had cross-sectional cerebrospinal fluid (CSF) α-synuclein measurement from seed-amplification assay as well as cross-sectional and longitudinal amyloid beta (Aβ) and tau levels (measured in CSF and/or by positron emission tomography). All analyses were adjusted for age, sex, and cognitive status. RESULTS: Across cohorts, the main biomarker associated with α-synuclein positivity at baseline was higher levels of Aβ pathology (all p values ≤ 0.02), but not tau. Looking at longitudinal measures of AD biomarkers, α-synuclein -positive participants had a statistically significant faster increase of Aβ load, although of modest magnitude (1.11 Centiloid/year, p = 0.02), compared to α-synuclein -negative participants in BioFINDER-2 but not in ADNI. DISCUSSION: We showed associations between concurrent misfolded α-synuclein and Aβ levels, providing in vivo evidence of links between these two molecular disease pathways in humans. HIGHLIGHTS: Amyloid beta (Aβ), but not tau, was associated with alpha-synuclein (α-synuclein) positivity. Such association was consistent across two cohorts, beyond the effect of age, sex, and cognitive status. α-synuclein-positive participants had a small, statistically significant faster increase in Aβ positron emission tomography levels in one of the two cohorts.","journal":"Alzheimer s & Dementia","year":2024,"id":423895,"datarank":0.7655977320009191,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.2888896574487271,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.2888896574487271,"corpus_percentile":73.73713932080142,"corpus_rank":3396,"citation_count":23,"citer_count":22,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.7285,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1219707,"name":"Angela Mammana","orcid":"0000-0002-6237-8784","position":1,"is_corresponding":false},{"id":260099,"name":"Laura E.M. Wisse","orcid":"0000-0001-7504-3943","position":2,"is_corresponding":false},{"id":227548,"name":"Marcello Rossi","orcid":"0000-0002-8125-6571","position":3,"is_corresponding":false},{"id":229338,"name":"Olof Strandberg","orcid":null,"position":4,"is_corresponding":false},{"id":226048,"name":"Ruben Smith","orcid":"0000-0001-7147-0112","position":5,"is_corresponding":false},{"id":230942,"name":"Niklas Mattsson","orcid":"0000-0002-8885-7724","position":6,"is_corresponding":false},{"id":230943,"name":"Shorena Janelidze","orcid":"0000-0003-2869-8378","position":7,"is_corresponding":false},{"id":230950,"name":"Sebastian Palmqvist","orcid":"0000-0002-9267-1930","position":8,"is_corresponding":false},{"id":569339,"name":"ADNI","orcid":null,"position":9,"is_corresponding":false},{"id":1220236,"name":"Alice Ticca","orcid":null,"position":10,"is_corresponding":false},{"id":230949,"name":"Erik Stomrud","orcid":"0000-0002-0841-5580","position":11,"is_corresponding":false},{"id":227562,"name":"Piero Parchi","orcid":"0000-0002-9444-9524","position":12,"is_corresponding":false},{"id":65584,"name":"Oskar Hansson","orcid":"0000-0001-8467-7286","position":13,"is_corresponding":false},{"id":561487,"name":"Alexa Pichet Binette","orcid":"0000-0001-5218-3337","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-19T01:58:01.889748Z","pmid":"39258841","pmcid":"PMC11567871","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":[]}