{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T01:02:43Z","timestamp":1784509363525,"version":"3.55.0"},"reference-count":163,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013254","name":"National College Students Innovation and Entrepreneurship Training Program","doi-asserted-by":"publisher","award":["S202610043026"],"award-info":[{"award-number":["S202610043026"]}],"id":[{"id":"10.13039\/501100013254","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Fundamental Research Funds for the Central Universities","award":["2025KYPT05"],"award-info":[{"award-number":["2025KYPT05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>With the growing of the global population aging, the comorbidity of cardiovascular disease (CVD) and Alzheimer\u2019s disease (AD) has gradually become a major contributor to global disease burden, with the two diseases exhibiting interacting pathological characteristics. This review summarizes the mechanisms underlying CVD-AD comorbidity, including cerebral hypoperfusion and protein aggregation, oxidative stress and inflammation, as well as metabolic disorders and genetic factors. We also assess the value of blood biomarkers in this comorbidity, such as p-tau217, NT-proBNP, NfL, GFAP, and miRNAs. We then review the role of exercise in ameliorating this comorbidity, integrating its potential mechanisms into five aspects: repairing cerebral hypoperfusion and endothelial injury, accelerating A\u03b2 clearance and inhibiting Tau protein hyperphosphorylation, reducing inflammation, protecting neuronal structure and the blood\u2013brain barrier, and improving metabolic disorder. We also analyze in detail the relationship between exercise targets and blood biomarkers. Finally, we discussed the impact and application of different exercise modalities in this comorbidity, concluding with suitable exercise prescriptions and relevant safety considerations for each modality, further organized the mainstream pharmacological and nutritional intervention strategies for CVD-AD comorbidity, and objectively explored their potential interactions when combined with exercise interventions. Future research should integrate multi-omics technologies and gradually refine clinical data on comorbidity, with the aim of developing more targeted, personalized exercise prescriptions for patients with comorbidities, thereby providing scientific theoretical guidance for early risk prevention and disease management in patients with co-occurring CVD and AD.<\/jats:p>","DOI":"10.3390\/cells15141284","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:47:32Z","timestamp":1784508452000},"page":"1284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Exercise in Cardiovascular Disease and Alzheimer\u2019s Disease Comorbidity: A Blood Biomarker Perspective"],"prefix":"10.3390","volume":"15","author":[{"given":"Yu","family":"Lu","sequence":"first","affiliation":[{"name":"School of Sport Science, Beijing Sport University, Beijing 100084, China"},{"name":"Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-1471","authenticated-orcid":false,"given":"Chunyan","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Sport Science, Beijing Sport University, Beijing 100084, China"},{"name":"Beijing Sports Nutrition Engineering Research Center, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6706-375X","authenticated-orcid":false,"given":"Pengyu","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Physical Education, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-0901","authenticated-orcid":false,"given":"Lijing","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China"},{"name":"China Institute of Sport and Health Science, Beijing Sport University, Beijing 100084, China"},{"name":"Key Laboratory for Performance Training & Recovery of General Administration of Sport, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","article-title":"Alzheimer\u2019s disease","volume":"388","author":"Scheltens","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.7150\/thno.81951","article-title":"High-intensity interval training ameliorates alzheimer\u2019s disease-like pathology by regulating astrocyte phenotype-associated AQP4 polarization","volume":"13","author":"Feng","year":"2023","journal-title":"Theranostics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1111\/j.1532-5415.2005.53360.x","article-title":"Dementia and Alzheimer\u2019s disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort","volume":"53","author":"Newman","year":"2005","journal-title":"J. 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