{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T16:09:11Z","timestamp":1775578151658,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centre of Postgraduate Medical Education","award":["501-1-031-22-21"],"award-info":[{"award-number":["501-1-031-22-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common cause of dementia and is characterized by progressive cognitive decline, \u03b2-amyloid accumulation, tau pathology, oxidative stress, and neuroinflammation. Increasing evidence suggests that metabolic dysregulation may contribute to AD pathogenesis. Glucagon-like peptide-2 (GLP-2), an intestinal peptide hormone, has demonstrated neuroprotective effects in preclinical models, potentially through anti-inflammatory and anti-apoptotic mechanisms. However, its role in human neurodegenerative disorders remains insufficiently understood. This study aimed to compare plasma GLP-2 concentrations between individuals with AD and cognitively healthy controls and to examine associations between GLP-2 levels, cognitive impairment severity, and metabolic parameters. Sixty-one patients with clinically diagnosed AD and twenty-three cognitively unimpaired controls were recruited. Plasma total GLP-2 concentrations were assessed at baseline in all participants and additionally at 6 and 12 months in a subgroup of 34 AD patients. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) scale. Group comparisons, subgroup analyses based on AD severity, repeated-measures analyses, Spearman correlations, and multivariable linear regression models (including age and clinical group) were performed. Plasma GLP-2 concentrations were significantly higher in AD patients than in controls, with a moderate effect size (Cohen\u2019s d \u2248 0.60). In severity-based subgroup analyses, both the mild and moderate-to-severe AD groups showed significantly higher GLP-2 levels than controls. Longitudinal analyses in AD patients (n = 34) showed no significant changes in GLP-2 concentrations over 12 months. Cognitive performance declined over time, with a significant reduction in MMSE from baseline to 6 months, whereas GLP-2 levels were not correlated with MMSE or CDR at any time point. GLP-2 levels correlated positively with body mass index (BMI), body weight, insulin, and HOMA-IR. In multivariable regression analysis, neither age nor clinical group independently predicted GLP-2 concentrations (both p &gt; 0.05). Plasma GLP-2 concentrations were higher in patients with AD than in cognitively healthy controls; however, GLP-2 levels were not associated with cognitive performance or its progression over 12 months. GLP-2 was positively related to markers of adiposity and insulin resistance, suggesting stronger links to metabolic status than to cognitive severity. Further studies are needed to clarify whether GLP-2 alterations in AD reflect compensatory mechanisms, metabolic factors, or disease-related pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms27031609","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:32:59Z","timestamp":1770395579000},"page":"1609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Potential Neuroprotective Role of GLP-2 in Alzheimer\u2019s Disease: Clinical Observations, Mechanistic Insights, and Comparison with GLP-1"],"prefix":"10.3390","volume":"27","author":[{"given":"Maciej","family":"Czarnecki","sequence":"first","affiliation":[{"name":"Neuroprotect Medical Center, 01-684 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6477-8485","authenticated-orcid":false,"given":"Agnieszka","family":"Baranowska-Bik","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-733X","authenticated-orcid":false,"given":"Anna","family":"Litwiniuk","sequence":"additional","affiliation":[{"name":"Department of Neuroendocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Kalisz","sequence":"additional","affiliation":[{"name":"Department of Neuroendocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Doma\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Neuroendocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kurdy\u0142a","sequence":"additional","affiliation":[{"name":"Neuroprotect Medical Center, 01-684 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Bik","sequence":"additional","affiliation":[{"name":"Department of Neuroendocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Nichols","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.2147\/NDT.S172285","article-title":"Alzheimer\u2019s disease and blood-based biomarkers\u2014Potential contexts of use","volume":"14","year":"2018","journal-title":"Neuropsychiatr. 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