{"doi":"10.1093/braincomms/fcad312","title":"CSF 14-3-3β is associated with progressive cognitive decline in Alzheimer’s disease","abstract":"Abstract Alzheimer’s disease is a neurodegenerative disorder characterized pathologically by amyloid-beta plaques, tau tangles and neuronal loss. In clinical practice, the 14-3-3 isoform beta (β) is a biomarker that aids in the diagnosis of sporadic Creutzfeldt–Jakob disease. Recently, a proteomics study found increased CSF 14-3-3β levels in Alzheimer’s disease patients, suggesting a potential link between CSF 14-3-3β and Alzheimer’s disease. Our present study aimed to further investigate the role of CSF 14-3-3β in Alzheimer’s disease by analysing the data of 719 participants with available CSF 14-3-3β measurements from the Alzheimer’s Disease Neuroimaging Initiative. Higher CSF 14-3-3β levels were observed in the mild cognitive impairment group compared to the cognitively normal group, with the highest CSF 14-3-3β levels in the Alzheimer’s disease dementia group. This study also found significant associations between CSF 14-3-3β levels and CSF biomarkers of p-tau, t-tau, pTau/Aβ42 ratios and GAP-43, as well as other Alzheimer’s disease biomarkers such as Aβ-PET. An early increase in CSF 14-3-3β levels was observed prior to Aβ-PET–positive status, and CSF 14-3-3β levels continued to rise after crossing the Aβ-PET positivity threshold before reaching a plateau. The diagnostic accuracy of CSF 14-3-3β (area under the receiver operating characteristic curve = 0.819) was moderate compared to other established Alzheimer’s disease biomarkers in distinguishing cognitively normal Aβ pathology–negative individuals from Alzheimer’s disease Aβ pathology–positive individuals. Higher baseline CSF 14-3-3β levels were associated with accelerated cognitive decline, reduced hippocampus volumes and declining fluorodeoxyglucose-PET values over a 4-year follow-up period. Patients with mild cognitive impairment and high CSF 14-3-3β levels at baseline had a significantly increased risk [hazard ratio = 2.894 (1.599–5.238), P < 0.001] of progression to Alzheimer’s disease dementia during follow-up. These findings indicate that CSF 14-3-3β may be a potential biomarker for Alzheimer’s disease and could provide a more comprehensive understanding of the underlying pathological changes of Alzheimer’s disease, as well as aid in the diagnosis and monitoring of disease progression.","journal":"Brain Communications","year":2023,"id":361435,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"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":871441,"name":"Loren Skudder‐Hill","orcid":"0000-0003-1182-3873","position":1,"is_corresponding":false},{"id":871442,"name":"Tomoko Toyota","orcid":"0000-0003-3114-0244","position":2,"is_corresponding":false},{"id":1010651,"name":"Zhe Huang","orcid":"0000-0002-3524-2806","position":3,"is_corresponding":false},{"id":871443,"name":"Wenshi Wei","orcid":"0000-0002-1184-3164","position":4,"is_corresponding":false},{"id":499444,"name":"Hiroaki Adachi","orcid":"0000-0002-9302-4663","position":5,"is_corresponding":false},{"id":229339,"name":"Alzheimer’s Disease Neuroimaging Initiative","orcid":null,"position":6,"is_corresponding":false},{"id":871440,"name":"Qiang Qiang","orcid":"0000-0002-9071-3236","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:14:10.680991Z","pmid":"38035365","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":[]}