{"doi":"10.1016/j.neurobiolaging.2025.10.005","title":"Hippocampal 1H-MR spectroscopy metabolites are linked to CSF tau pathology in cognitively unimpaired older adults along the Alzheimer’s continuum","abstract":"Relationships between Alzheimer’s disease (AD) pathologies in cognitively unimpaired adults and in vivo neurometabolic properties measured directly from the hippocampus, a vulnerable region early along the AD continuum, are not well-understood in the earliest stages of AD. In a 3T 1 H-MRS study, we assessed age and AD-related changes in estimates of absolute concentrations of neurometabolites in the right hippocampus. Participants included older adults (age range: 60-85, n=19) primarily cognitively unimpaired (CU, n=16), as well as some with cognitive impairment (n=3). All participants previously received a lumbar puncture for AD disease staging from cerebrospinal fluid (CSF) AD biomarkers (Aβ42, p-tau181 and t-tau), where all were amyloid positive (A+) and most had subthreshold tau pathology (T-). Hippocampal 1 H-MRS metabolites included total N-acetylaspartate (tNAA), myo-inositol (mIns), total creatine (tCr) and total choline (tCho). Regression analyses were performed for assessing relationships among CSF biomarkers, age, and 1 H-MRS metabolites measured as tissue-corrected estimates of absolute concentrations (millimoles/kilogram) and as ratios (/tCr and tNAA/mIns). We identified age-related decreases to mIns/tCr, where estimated absolute concentrations revealed that tCr increased while mIns remained stable. Concentrations for tNAA and mIns were positively associated with CSF p-tau181 and t-tau. Levels of tCr and tCho were not associated with any CSF biomarkers. Overall, our results demonstrate that sub-threshold tau pathologies in cognitively unimpaired A+ individuals are associated with hippocampal metabolite changes related to neural metabolism and glial reactivity early in disease progression.","journal":"Neurobiology of Aging","year":2025,"id":579498,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9469,"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":995647,"name":"Casey R. Vanderlip","orcid":"0000-0002-8233-5829","position":1,"is_corresponding":false},{"id":1323541,"name":"Sierra Wright","orcid":null,"position":2,"is_corresponding":false},{"id":1038976,"name":"Lorena Sordo","orcid":"0000-0002-7016-6706","position":3,"is_corresponding":false},{"id":270466,"name":"Elizabeth Head","orcid":"0000-0003-1115-6396","position":4,"is_corresponding":false},{"id":260105,"name":"Craig E.L. Stark","orcid":"0000-0002-9334-8502","position":5,"is_corresponding":false},{"id":1490090,"name":"Jessica N Lingad","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:58:30.282164Z","pmid":"41192405","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":[]}