{"doi":"10.1002/alz.70080","title":"Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline","abstract":"INTRODUCTION: Baseline and longitudinal characteristics of cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) and plasma neurofilament light (NfL) and how they correlate interactively with neurodegeneration and cognitive decline in Alzheimer's disease (AD) are not fully understood. METHODS: We investigated dynamic changes of CSF GAP-43 and plasma NfL across different AD stages and their association with longitudinal neurodegeneration and cognitive decline up to 12 years. RESULTS: Individuals with hippocampal atrophy, AD-signature cortical thinning, or hypometabolism (N+) had faster plasma NfL increase rates than healthy individuals, regardless of amyloid/tau status. In contrast, none of these N+ imaging indicators correlated with more rapid increases in CSF GAP-43. Furthermore, CSF GAP-43 and plasma NfL synergistically predicted subsequent gray matter atrophy, cortical thinning, hypometabolism of the middle temporal region, and cognition. DISCUSSION: CSF GAP-43-associated presynaptic loss indicates tau-dependent early neurodegeneration, whereas the axonal degeneration indicated by plasma NfL is a relatively late atrophy/hypometabolism-associated fluid neurodegeneration biomarker. HIGHLIGHTS: Plasma neurofilament light (NfL) was increased in N+ or cognitively impaired individuals. Increases in tau-dependent cerebrospinal fluid CSF growth-associated protein 43 (GAP-43) before imaging neurodegeneration indicators. CSF GAP-43 and plasma NfL are synergistically related to longitudinal neurodegeneration. CSF GAP-43 and plasma NfL are synergistically related to longitudinal cognitive decline.","journal":"Alzheimer s & Dementia","year":2025,"id":514332,"datarank":0.3703058784462869,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.040722191845853885,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.040722191845853885,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":6,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1090187,"name":"Chenghui Ye","orcid":null,"position":1,"is_corresponding":false},{"id":313753,"name":"Anqi Li","orcid":"0000-0003-1409-1858","position":2,"is_corresponding":false},{"id":1235234,"name":"Pan Sun","orcid":"0000-0002-7135-2631","position":3,"is_corresponding":false},{"id":881828,"name":"Guoyu Lan","orcid":"0000-0003-2925-1738","position":4,"is_corresponding":false},{"id":1377532,"name":"Laihong Zhang","orcid":null,"position":5,"is_corresponding":false},{"id":15052,"name":"Xin Zhou","orcid":"0000-0002-1407-7952","position":6,"is_corresponding":false},{"id":1376913,"name":"Liemin Zhou","orcid":"0000-0001-8470-8871","position":7,"is_corresponding":false},{"id":693576,"name":"Zhen Liu","orcid":"0000-0002-5978-3412","position":8,"is_corresponding":false},{"id":277015,"name":"Tengfei Guo","orcid":"0000-0003-2982-0865","position":9,"is_corresponding":false},{"id":300139,"name":"for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":10,"is_corresponding":false},{"id":889959,"name":"Dai Shi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:48:29.165853Z","pmid":"40495607","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":[]}