{"doi":"10.3233/jad-220447","title":"Nonobese Male Patients with Alzheimer’s Disease Are Vulnerable to Decrease in Plasma Leptin","abstract":"<jats:p>Background: Metabolic dysfunction links to cognitive deficits in Alzheimer’s disease (AD). Leptin is an anti-obesity hormone that modulates energy homeostasis and memory function. Although leptin deregulation is implicated in mouse models of AD-like brain pathology, clinical studies have shown inconsistent results regarding an association of leptin with the development of this neurodegenerative disorder. Objective: We investigated the changes of plasma leptin and the correlation of sex-stratified circulating leptin with cognitive performance, AD-related biological markers, and metabolic status in patients with AD and cognitively unimpaired (CU) counterparts. Methods: We used nonobese AD patients and CU controls in a University of Kansas Medical Center (KUMC) cohort. Plasma leptin levels, circulating AD-related molecules and metabolic profiles were examined and analyzed. Results: In contrast to unchanged circulating leptin in females, male patients exhibited decreased plasma leptin levels compared with male CU counterparts. Moreover, plasma leptin showed no correlation with cognitive performance and AD blood biomarkers in patients with either sex. Of note, females but not males demonstrated an association of plasma leptin with body mass index, high density lipoprotein-cholesterol and its ratio with total cholesterol and triglycerides. Conclusion: Our findings suggest that leptin deficiency is associated with nonobese male AD patients, supporting systemic dysmetabolism in the development of this neurodegenerative disorder in certain populations. Although plasma leptin may have limited capacity to reflect disease severity or progression, future mechanistic studies on the regulation of leptin in nonobese patients with AD would deepen our understanding of the sex-related disparity of AD etiopathogenesis.</jats:p>","journal":"Journal of Alzheimer's Disease","year":2022,"id":643398,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":921324,"name":"Tienju Wang","orcid":null,"position":1,"is_corresponding":false},{"id":590056,"name":"Kun Jia","orcid":"0000-0002-7906-8109","position":2,"is_corresponding":false},{"id":1167575,"name":"Lan Guo","orcid":"0000-0001-7097-4749","position":3,"is_corresponding":false},{"id":107455,"name":"Russell H. Swerdlow","orcid":"0000-0003-2948-7230","position":4,"is_corresponding":false},{"id":298781,"name":"Heng Du","orcid":"0000-0001-9067-0910","position":5,"is_corresponding":false},{"id":236412,"name":"Jing Tian","orcid":"0000-0002-9821-3295","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Nonobese Male Patients with Alzheimer’s Disease Are Vulnerable to Decrease in Plasma Leptin","abstract":"<jats:p>Background: Metabolic dysfunction links to cognitive deficits in Alzheimer’s disease (AD). Leptin is an anti-obesity hormone that modulates energy homeostasis and memory function. Although leptin deregulation is implicated in mouse models of AD-like brain pathology, clinical studies have shown inconsistent results regarding an association of leptin with the development of this neurodegenerative disorder. Objective: We investigated the changes of plasma leptin and the correlation of sex-stratified circulating leptin with cognitive performance, AD-related biological markers, and metabolic status in patients with AD and cognitively unimpaired (CU) counterparts. Methods: We used nonobese AD patients and CU controls in a University of Kansas Medical Center (KUMC) cohort. Plasma leptin levels, circulating AD-related molecules and metabolic profiles were examined and analyzed. Results: In contrast to unchanged circulating leptin in females, male patients exhibited decreased plasma leptin levels compared with male CU counterparts. Moreover, plasma leptin showed no correlation with cognitive performance and AD blood biomarkers in patients with either sex. Of note, females but not males demonstrated an association of plasma leptin with body mass index, high density lipoprotein-cholesterol and its ratio with total cholesterol and triglycerides. Conclusion: Our findings suggest that leptin deficiency is associated with nonobese male AD patients, supporting systemic dysmetabolism in the development of this neurodegenerative disorder in certain populations. Although plasma leptin may have limited capacity to reflect disease severity or progression, future mechanistic studies on the regulation of leptin in nonobese patients with AD would deepen our understanding of the sex-related disparity of AD etiopathogenesis.</jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35723107","pmcid":"PMC9553411","openalex_id":"https://openalex.org/W4282828684","authors":[],"funders":[{"funder_name":"NIA NIH HHS","grant_id":"R01 AG075108","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG053588","title":null},{"funder_name":"NIA NIH HHS","grant_id":"P30 AG035982","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG059753","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01AG075108-02","title":"mtDNA leakage and STING-dependent microglial innate immune response in Alzheimer's disease"},{"funder_name":"National Institutes of Health","grant_id":"5R01AG059753-06","title":"GHSR1a and Hippocampal Pathology in Alzheimer's Disease"},{"funder_name":"National Institutes of Health","grant_id":"5P30AG035982-05","title":"Administrative Core"},{"funder_name":"National Institutes of Health","grant_id":"5R01AG053588-04","title":"Mitochondrial ATP Synthase Dysfunction and Synaptic Stress in Alzheimer's Disease"}],"total_grants":8,"fwci":0.6937,"citation_percentile":0.61886949,"influential_citations":0,"citation_trend":[{"year":2023,"count":3},{"year":2024,"count":1},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://kuscholarworks.ku.edu/bitstreams/409a39bb-2cc3-47cb-a51b-28d5e0328ec9/download","host_type":"repository"},{"url":"https://kuscholarworks.ku.edu/bitstreams/409a39bb-2cc3-47cb-a51b-28d5e0328ec9/download","host_type":"repository"},{"url":"https://content.iospress.com/download?id=10.3233/JAD-220447","host_type":"publisher"},{"url":"https://doi.org/10.3233/jad-220447","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35723107","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9553411","host_type":"repository"},{"url":"http://hdl.handle.net/1808/33983","host_type":"Unpaywall"},{"url":"https://doi.org/https://doi.org/10.3233/JAD-220447","host_type":""}],"fields_of_study":["Regulation of Appetite and Obesity","Olfactory and Sensory Function Studies","Alzheimer's disease research and treatments","03 medical and health sciences","0302 clinical medicine","Alzheimer Disease","Animals","Biomarkers","Body Mass Index","Cholesterol, HDL","Female","Humans","Leptin","Mice"],"mesh_terms":["Alzheimer Disease","Animals","Female","Humans","Cholesterol, HDL","Biomarkers","Body Mass Index","Leptin","Mice"],"keywords":["Leptin","Internal medicine","Endocrinology","Medicine","Disease","Energy homeostasis","Body mass index","Hormone","Obesity","Cholesterol","Metabolism","Sex","Alzheimer’s disease","Blood Biomarker","Plasma Leptin","Cholesterol, HDL","610","Mice","Alzheimer Disease","616","Animals","Humans","Female","Biomarkers"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. 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