{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:15:21Z","timestamp":1777392921463,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,6,25]]},"abstract":"<jats:p>Background: Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer\u2019s disease (AD), sharing similar pathophysiological traits like impaired insulin signaling. Objective: To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology. Methods: A total of 304 participants were included in the Alzheimer\u2019s Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages. Results: In the non-demented group, amyloid-\u03b2 (A\u03b2)+ participants (e.g., as reflected by CSF A\u03b242) exhibited significantly lower plasma insulin levels compared to non-demented A\u03b2\u2013participants (p\u200a&lt;\u200a0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF A\u03b242 and pTau181 levels) when compared to the A\u2013T\u2013 group within the non-dementia group (p\u200a=\u200a0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF A\u03b242 levels (p\u200a&lt;\u200a0.001) across all participants. This association was particularly significant in the A\u03b2\u2013group (p\u200a=\u200a0.002) and among non-demented individuals (p\u200a&lt;\u200a0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF A\u03b242 (p\u200a=\u200a0.006), whereas baseline CSF A\u03b242 did not show a similar correlation with changes in plasma insulin over time. Conclusions: These findings suggest an association between plasma insulin and early A\u03b2 pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early A\u03b2 pathology.<\/jats:p>","DOI":"10.3233\/jad-240289","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T11:27:37Z","timestamp":1717759657000},"page":"321-332","source":"Crossref","is-referenced-by-count":4,"title":["Plasma Insulin Predicts Early Amyloid-\u03b2 Pathology Changes in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"100","author":[{"given":"Yu-Han","family":"Chen","sequence":"first","affiliation":[{"name":"The First Clinical Medical School, Hebei North University, Zhangjiakou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi-Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Hebei North University, Hebei, Zhangjiakou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Qi","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-240289_ref1","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer disease: An update on pathobiology and treatment strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"10.3233\/JAD-240289_ref2","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"10.3233\/JAD-240289_ref3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12929-023-00976-6","article-title":"Clinical trials of new drugs for Alzheimer disease: A 2020\u20132023 update","volume":"30","author":"Huang","year":"2023","journal-title":"J Biomed Sci"},{"key":"10.3233\/JAD-240289_ref4","doi-asserted-by":"crossref","first-page":"1130253","DOI":"10.3389\/fnagi.2023.1130253","article-title":"Natural bioactive compounds in Alzheimer\u2019s disease: From the perspective of type 3 diabetes mellitus","volume":"15","author":"Huang","year":"2023","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-240289_ref5","doi-asserted-by":"crossref","first-page":"3982","DOI":"10.1038\/s41380-023-02267-w","article-title":"Tau suppresses microtubule-regulated pancreatic insulin secretion","volume":"28","author":"Mangiafico","year":"2023","journal-title":"Mol Psychiatry"},{"key":"10.3233\/JAD-240289_ref6","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1001\/jama.2021.4001","article-title":"Association between age at diabetes onset and subsequent risk of dementia","volume":"325","author":"Barbiellini Amidei","year":"2021","journal-title":"JAMA"},{"key":"10.3233\/JAD-240289_ref7","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the Lancet Commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"10.3233\/JAD-240289_ref8","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1212\/WNL.0000000000001982","article-title":"Type 2 diabetes mellitus and biomarkers of neurodegeneration","volume":"85","author":"Moran","year":"2015","journal-title":"Neurology"},{"key":"10.3233\/JAD-240289_ref9","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1212\/WNL.0000000000000269","article-title":"Association of type 2 diabetes with brain atrophy and cognitive impairment","volume":"82","author":"Roberts","year":"2014","journal-title":"Neurology"},{"key":"10.3233\/JAD-240289_ref10","doi-asserted-by":"crossref","first-page":"15287","DOI":"10.3390\/ijms232315287","article-title":"Type 2 diabetes mellitus and Alzheimer\u2019s disease: Shared molecular mechanisms and potential common therapeutic targets","volume":"23","author":"Hamz\u00e9","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.3233\/JAD-240289_ref11","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.3390\/cells10051236","article-title":"Insulin resistance and diabetes mellitus in Alzheimer\u2019s disease","volume":"10","author":"Burillo","year":"2021","journal-title":"Cells"},{"key":"10.3233\/JAD-240289_ref12","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1007\/s12035-019-01858-5","article-title":"Alzheimer\u2019s disease and diabetes: Insulin signaling as the bridge linking two pathologies","volume":"57","author":"Shieh","year":"2020","journal-title":"Mol Neurobiol"},{"key":"10.3233\/JAD-240289_ref13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41583-022-00558-9","article-title":"Impaired insulin signalling and allostatic load in Alzheimer disease","volume":"23","author":"De Felice","year":"2022","journal-title":"Nat Rev Neurosci"},{"key":"10.3233\/JAD-240289_ref14","doi-asserted-by":"crossref","first-page":"e2220684120","DOI":"10.1073\/pnas.2220684120","article-title":"Loss of insulin signaling in astrocytes exacerbates Alzheimer-like phenotypes in a 5xFAD mouse model","volume":"120","author":"Chen","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-240289_ref15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.exger.2016.12.019","article-title":"Glucose tolerance and insulin sensitivity are impaired in APP\/PS1 transgenic mice prior to amyloid plaque pathogenesis and cognitive decline","volume":"88","author":"Macklin","year":"2017","journal-title":"Exp Gerontol"},{"key":"10.3233\/JAD-240289_ref16","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3233\/JAD-180707","article-title":"Impaired glucose tolerance and reduced plasma insulin precede decreased AKT phosphorylation and GLUT3 translocation in the hippocampus of old 3xTg-AD mice","volume":"68","author":"Griffith","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-240289_ref17","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3233\/JAD-2005-8304","article-title":"Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer\u2019s disease: Link to brain reductions in acetylcholine","volume":"8","author":"Rivera","year":"2005","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-240289_ref18","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1172\/JCI59903","article-title":"Demonstrated brain insulin resistance in Alzheimer\u2019s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline","volume":"122","author":"Talbot","year":"2012","journal-title":"J Clin Invest"},{"key":"10.3233\/JAD-240289_ref19","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1001\/jamaneurol.2013.284","article-title":"Glucose intolerance, insulin resistance, and pathological features of Alzheimer disease in the Baltimore Longitudinal Study of Aging","volume":"70","author":"Thambisetty","year":"2013","journal-title":"JAMA Neurol"},{"key":"10.3233\/JAD-240289_ref20","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.jalz.2014.03.011","article-title":"Insulin resistance predicts brain amyloid deposition in late middle-aged adults","volume":"11","author":"Willette","year":"2015","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240289_ref21","doi-asserted-by":"crossref","first-page":"106385","DOI":"10.1016\/j.nbd.2023.106385","article-title":"Midlife insulin resistance, APOE genotype, and change in late-life brain beta-amyloid accumulation \u2013 A 5-year follow-up [11C]PIB-PET study","volume":"190","author":"Pietil\u00e4","year":"2024","journal-title":"Neurobiol Dis"},{"key":"10.3233\/JAD-240289_ref22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13195-017-0258-6","article-title":"The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer\u2019s pathology","volume":"9","author":"Westwood","year":"2017","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-240289_ref23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.neurobiolaging.2017.07.004","article-title":"Differential effects of blood insulin and HbA1c on cerebral amyloid burden and neurodegeneration in nondiabetic cognitively normal older adults","volume":"59","author":"Byun","year":"2017","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-240289_ref24","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.3233\/JAD-200145","article-title":"Association of peripheral insulin resistance and other markers of type 2 diabetes mellitus with brain amyloid deposition in healthy individuals at risk of dementia","volume":"76","author":"Pekkala","year":"2020","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-240289_ref25","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1212\/WNL.0b013e3181cb3e25","article-title":"Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI): Clinical characterization","volume":"74","author":"Petersen","year":"2010","journal-title":"Neurology"},{"key":"10.3233\/JAD-240289_ref26","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s12974-022-02679-5","article-title":"Interleukin-3 is associated with sTREM2 and mediates the correlation between amyloid-\u03b2 and tau pathology in Alzheimer\u2019s disease","volume":"19","author":"Wang","year":"2022","journal-title":"J Neuroinflammation"},{"key":"10.3233\/JAD-240289_ref27","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.jalz.2015.05.003","article-title":"The Alzheimer\u2019s Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans","volume":"11","author":"Kang","year":"2015","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240289_ref28","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1210\/jcem-24-10-1076","article-title":"Plasma insulin response to oral and intravenous glucose administration","volume":"24","author":"Elrick","year":"1964","journal-title":"J Clin Endocrinol Metab"},{"key":"10.3233\/JAD-240289_ref29","doi-asserted-by":"crossref","first-page":"812","DOI":"10.7326\/0003-4819-79-6-812","article-title":"Plasma insulin and glucose profiles in normal, obese, and diabetic persons","volume":"79","author":"Genuth","year":"1973","journal-title":"Ann Intern Med"},{"key":"10.3233\/JAD-240289_ref30","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3803\/EnM.2013.28.3.207","article-title":"Variation in serum creatinine level is correlated to risk of type 2 diabetes","volume":"28","author":"Moon","year":"2013","journal-title":"Endocrinol Metab"},{"key":"10.3233\/JAD-240289_ref31","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1177\/0271678X17709709","article-title":"Insulin differentially affects the distribution kinetics of amyloid beta 40 and 42 in plasma and brain","volume":"38","author":"Swaminathan","year":"2018","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.3233\/JAD-240289_ref32","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1212\/01.wnl.0000216274.58185.09","article-title":"Differential modulation of plasma beta-amyloid by insulin in patients with Alzheimer disease","volume":"66","author":"Kulstad","year":"2006","journal-title":"Neurology"},{"key":"10.3233\/JAD-240289_ref33","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrneurol.2017.185","article-title":"Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums","volume":"14","author":"Arnold","year":"2018","journal-title":"Nat Rev Neurol"},{"key":"10.3233\/JAD-240289_ref34","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240289_ref35","doi-asserted-by":"crossref","first-page":"9766","DOI":"10.1038\/s41598-017-09577-4","article-title":"Insulin resistance is associated with reductions in specific cognitive domains and increases in CSF tau in cognitively normal adults","volume":"7","author":"Laws","year":"2017","journal-title":"Sci Rep"},{"key":"10.3233\/JAD-240289_ref36","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.neurobiolaging.2022.03.004","article-title":"Insulin resistance, cognition and Alzheimer\u2019s disease biomarkers: Evidence that CSF A\u03b242 moderates the association between insulin resistance and increased CSF tau levels","volume":"114","author":"Woodfield","year":"2022","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-240289_ref37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s13195-023-01180-2","article-title":"The relationship of insulin resistance and diabetes to tau PET SUVR in middle-aged to older adults","volume":"15","author":"Ennis","year":"2023","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-240289_ref38","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/brain\/awac354","article-title":"Diabetes and hypertension are related to amyloid-beta burden in the population-based Rotterdam Study","volume":"146","author":"van Arendonk","year":"2023","journal-title":"Brain"},{"key":"10.3233\/JAD-240289_ref39","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13024-019-0315-7","article-title":"Differential effects of diet- and genetically-induced brain insulin resistance on amyloid pathology in a mouse model of Alzheimer\u2019s disease","volume":"14","author":"Wakabayashi","year":"2019","journal-title":"Mol Neurodegener"},{"key":"10.3233\/JAD-240289_ref40","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: The amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"key":"10.3233\/JAD-240289_ref41","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S1474-4422(20)30071-5","article-title":"Blood phosphorylated tau 181 as a biomarker for Alzheimer\u2019s disease: A diagnostic performance and prediction modelling study using data from four prospective cohorts","volume":"19","author":"Karikari","year":"2020","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-240289_ref42","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1038\/s41591-023-02505-2","article-title":"Emerging diagnostics and therapeutics for Alzheimer disease","volume":"29","author":"Self","year":"2023","journal-title":"Nat Med"},{"key":"10.3233\/JAD-240289_ref43","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1002\/alz.12997","article-title":"Differences between ante mortem Alzheimer\u2019s disease biomarkers in predicting neuropathology at autopsy","volume":"19","author":"Wang","year":"2023","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240289_ref44","doi-asserted-by":"crossref","first-page":"5805","DOI":"10.1002\/alz.13455","article-title":"The potential clinical value of plasma biomarkers in Alzheimer\u2019s disease","volume":"19","author":"Blennow","year":"2023","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240289_ref45","doi-asserted-by":"crossref","first-page":"5620","DOI":"10.1002\/alz.13318","article-title":"Longitudinal blood biomarker trajectories in preclinical Alzheimer\u2019s disease","volume":"19","author":"Yakoub","year":"2023","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240289_ref46","doi-asserted-by":"crossref","first-page":"5151","DOI":"10.1002\/alz.13112","article-title":"Improved multimodal prediction of progression from MCI to Alzheimer\u2019s disease combining genetics with quantitative brain MRI and cognitive measures","volume":"19","author":"Reas","year":"2023","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240289_ref47","doi-asserted-by":"crossref","first-page":"7226","DOI":"10.1523\/JNEUROSCI.0071-23.2023","article-title":"Genetic reduction of insulin signaling mitigates amyloid-\u03b2 deposition by promoting expression of extracellular matrix proteins in the brain","volume":"43","author":"Sano","year":"2023","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-240289_ref48","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1038\/s41467-020-15436-0","article-title":"Cerebrospinal fluid pTau217 performs better than pTau181 as a biomarker of Alzheimer\u2019s disease","volume":"11","author":"Janelidze","year":"2020","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-240289_ref49","doi-asserted-by":"crossref","first-page":"e1681","DOI":"10.1212\/WNL.0000000000012727","article-title":"Comparing the clinical utility and diagnostic performance of CSF P-Tau181, P-Tau217, and P-Tau231 assays","volume":"97","author":"Leuzy","year":"2021","journal-title":"Neurology"},{"key":"10.3233\/JAD-240289_ref50","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s43587-023-00471-5","article-title":"A two-step workflow based on plasma pTau217 to screen for amyloid \u03b2 positivity with further confirmatory testing only in uncertain cases","volume":"3","author":"Brum","year":"2023","journal-title":"Nat Aging"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-240289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:58:28Z","timestamp":1777370308000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-240289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,25]]},"references-count":50,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3233\/jad-240289","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,25]]}}}