{"doi":"10.3389/fnagi.2022.941927","title":"Early increase of cerebrospinal fluid 14-3-3ζ protein in the alzheimer's disease continuum","abstract":"Background: The earlier research has shown that the 14-3-3ζ is increased in neurofibrillary tangles (NFTs) of human Alzheimer's disease (AD) brains and stimulates the tau phosphorylation. Cerebrospinal fluid (CSF) 14-3-3ζ along the AD continuum remains to be explored. Methods: We analyzed 113 cognitive normal (CN) controls, 372 patients with mild cognitive impairment (MCI), and 225 patients with AD dementia from the Alzheimer's Disease Neuroimaging Initiative database. CSF 14-3-3ζ protein was measured by Mass Spectrometry. Results: We observed higher CSF 14-3-3ζ in the MCI group vs. the CN group and in the AD group vs. the MCI or CN group. The 14-3-3ζ was able to distinguish AD from CN and MCI. High 14-3-3ζ predicted conversion from MCI to AD. In CSF, phosphorylated tau at threonine 181 and total-tau were associated with 14-3-3ζ in MCI and AD groups, and beta-amyloid (Aβ) 42 correlated with 14-3-3ζ in the MCI group. Baseline high 14-3-3ζ was associated with cognitive decline, brain atrophy, glucose hypometabolism, and Aβ deposition in MCI and AD at baseline and follow-up. Conclusion: Our findings revealed the potential diagnostic and prognostic utility of CSF 14-3-3ζ in the AD continuum. The 14-3-3ζ could be a promising therapeutic target for the intervention of AD.","journal":"Frontiers in Aging Neuroscience","year":2022,"id":253654,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8936,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":899623,"name":"Yuanyuan Lu","orcid":"0000-0002-4628-3195","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T00:24:59.596040Z","pmid":"35966774","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":[]}