{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:58:58Z","timestamp":1777395538788,"version":"3.51.4"},"reference-count":31,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,6,29]]},"abstract":"<jats:p>Background: Emerging evidence suggests a role for orthostatic hypotension (OH) in contributing to the progression of Alzheimer\u2019s disease (AD). The exosomes in the blood can reflect the pathological changes in the brain. Objective: To investigate whether neural-derived plasma exosomes pathogenic proteins of AD levels are associated with OH in diabetes mellitus (DM) patients. Methods: There were 274 subjects without dementia included in the study: 81 control participants (controls), 101 normotensive patients with DM without OH, and 92 patients with DM and neurogenic OH (DMOH). Neural-derived exosomal proteins were measured by ELISA kits for amyloid-\u03b2 (A\u03b2) and tau. Results: The neural-derived exosome levels of A\u03b242, total tau (T-tau), and tau phosphorylated at threonine 181 (P-T181-tau) in the DM with OH group were higher than those in the DM and control groups. Multivariable linear regression analysis showed that the presence of OH in patients with DM was associated with elevated exosomal A\u03b242 (\u03b2=\u200a0.172, p\u200a=\u200a0.018), T-tau (\u03b2=\u200a0.159, p\u200a=\u200a0.030), and P-T181-tau (\u03b2=\u200a0.220, p\u200a=\u200a0.003) levels after adjustment for age, sex, APOE \u025b4, duration of type 2 diabetes, HbA1c, and cardiovascular risk factors. Furthermore, the levels of A\u03b242, T-tau, and P-T181-tau in neural-derived exosomes were correlated with HIF-1\u03b1 levels and the drop in mean cerebral blood flow velocity from the supine to upright position. Conclusion: The presence of OH in DM patients was independently associated with elevated the A\u03b242, T-tau, and P-T181-tau levels in neural-derived plasma exosomes. Cerebral hypoperfusion from DM with OH are likely candidate mechanisms.<\/jats:p>","DOI":"10.3233\/jad-210216","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T13:54:44Z","timestamp":1621346084000},"page":"261-272","source":"Crossref","is-referenced-by-count":21,"title":["Altered Amyloid-\u03b2 and Tau Proteins in Neural-Derived Plasma Exosomes of Type 2 Diabetes Patients with Orthostatic Hypotension"],"prefix":"10.1177","volume":"82","author":[{"given":"Jinbiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shukun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tengqun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hairong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenguang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-210216_ref1","doi-asserted-by":"crossref","DOI":"10.1177\/2042018819826890","article-title":"Diagnosing and managing diabetic somatic and autonomic neuropathy","volume":"10","author":"Azmi","year":"2019","journal-title":"Ther Adv Endocrinol Metab"},{"key":"10.3233\/JAD-210216_ref2","doi-asserted-by":"crossref","first-page":"e1002143","DOI":"10.1371\/journal.pmed.1002143","article-title":"Orthostatic hypotension and the long-term risk of dementia: A population-based study","volume":"13","author":"Wolters","year":"2016","journal-title":"PLoS Med"},{"key":"10.3233\/JAD-210216_ref3","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3233\/JAD-190402","article-title":"Orthostatic hypotension: An important risk factor for clinical progression to mild cognitive impairment or dementia. 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