{"doi":"10.3390/endocrines5020014","title":"Biomarkers of Neurodegeneration and Alzheimer’s Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study","abstract":"Adult-onset diabetes increases one’s risk of neurodegenerative disease including Alzheimer’s disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aβ40, Aβ42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aβ40, Aβ42, and GFAP, and higher pTau181 compared to controls (p < 0.05), a pattern persisting into adulthood (p < 0.001). All biomarkers showed significant increases from adolescence to adulthood in Y-DM (p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases.","journal":"Endocrines","year":2024,"id":460940,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7511,"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":417379,"name":"Christina Coughlan","orcid":"0000-0002-7229-7056","position":1,"is_corresponding":false},{"id":471935,"name":"Brianne M. Bettcher","orcid":"0000-0001-8311-1985","position":2,"is_corresponding":false},{"id":667637,"name":"MEGHAN E. PAULEY","orcid":"0000-0002-5699-7108","position":3,"is_corresponding":false},{"id":505130,"name":"Jeongchul Kim","orcid":"0000-0002-2369-4653","position":4,"is_corresponding":false},{"id":247937,"name":"Petter Bjornstad","orcid":"0000-0002-5160-2947","position":5,"is_corresponding":false},{"id":1289514,"name":"BENJAMIN S. RAJIC","orcid":null,"position":6,"is_corresponding":false},{"id":1289051,"name":"Jennifer Truong","orcid":"0000-0003-0255-0287","position":7,"is_corresponding":false},{"id":1136696,"name":"Christopher Bell","orcid":"0000-0002-7706-0912","position":8,"is_corresponding":false},{"id":445411,"name":"Ye Ji Choi","orcid":"0000-0002-0167-175X","position":9,"is_corresponding":false},{"id":34922,"name":"Keenan A. Walker","orcid":"0000-0002-5989-9853","position":10,"is_corresponding":false},{"id":417385,"name":"Huntington Potter","orcid":"0000-0002-4051-2516","position":11,"is_corresponding":false},{"id":342444,"name":"Angela D. Liese","orcid":"0000-0002-7022-0178","position":12,"is_corresponding":false},{"id":249641,"name":"Dana Dabelea","orcid":"0000-0001-9514-8929","position":13,"is_corresponding":false},{"id":406157,"name":"Christopher T. Whitlow","orcid":"0000-0003-2392-8293","position":14,"is_corresponding":false},{"id":387898,"name":"Allison Shapiro","orcid":"0000-0001-8334-974X","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:04:07.925246Z","pmid":"38764894","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":[]}