{"doi":"10.3233/jad-201293","title":"Could Altered Evoked Pain Responsiveness Be a Phenotypic Biomarker for Alzheimer’s Disease Risk? A Cross-Sectional Analysis of Cognitively Healthy Individuals","abstract":"BACKGROUND: This study evaluated whether the apolipoprotein ɛ4 (APOE4) allele, a genetic marker associated with increased risk of developing late-onset Alzheimer's disease (AD), was associated with differences in evoked pain responsiveness in cognitively healthy subjects. OBJECTIVE: The aim was to determine whether individuals at increased risk of late-onset AD based on APOE allele genotype differ phenotypically in their response to experimentally-induced painful stimuli compared to those who do not have at least one copy of the ɛ4 allele. METHODS: Forty-nine cognitively healthy subjects aged 30-89 years old with the APOE4 allele (n = 12) and without (n = 37) were assessed for group differences in pain thresholds and affective (unpleasantness) responses to experimentally-induced thermal pain stimuli. RESULTS: Statistically significant main effects of APOE4 status were observed for both the temperature at which three different pain intensity percepts were reached (p = 0.040) and the level of unpleasantness associated with each (p = 0.014). APOE4 positive participants displayed lower overall pain sensitivity than those who were APOE4 negative and also greater overall levels of pain unpleasantness regardless of intensity level. CONCLUSION: Cognitively healthy APOE4 carriers at increased risk of late-onset AD demonstrated reduced thermal pain sensitivity but greater unpleasantness to thermal pain stimuli relative to individuals at lower risk of late-onset AD. These results suggest that altered evoked pain perception could potentially be used as a phenotypic biomarker of late-onset AD risk prior to disease onset. Additional studies of this issue may be warranted.","journal":"Journal of Alzheimer s Disease","year":2020,"id":85486,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":437393,"name":"Michael A. Carter","orcid":"0000-0002-1291-1050","position":1,"is_corresponding":false},{"id":318467,"name":"Mary S. Dietrich","orcid":"0000-0003-4474-0767","position":2,"is_corresponding":false},{"id":437394,"name":"Ronald L. Cowan","orcid":"0000-0002-0041-0670","position":3,"is_corresponding":false},{"id":318468,"name":"Stephen Bruehl","orcid":"0000-0003-2264-4758","position":4,"is_corresponding":false},{"id":437395,"name":"Todd B. Monroe","orcid":"0000-0003-3156-5808","position":5,"is_corresponding":false},{"id":437392,"name":"Raymond R. Romano","orcid":"0000-0001-6121-8263","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-18T21:58:16.217017Z","pmid":"33337380","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":[]}