Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China.
Department of Endocrinology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China.
J Alzheimers Dis. 2021;82(1):261-272. doi: 10.3233/JAD-210216.
Emerging evidence suggests a role for orthostatic hypotension (OH) in contributing to the progression of Alzheimer's disease (AD). The exosomes in the blood can reflect the pathological changes in the brain.
To investigate whether neural-derived plasma exosomes pathogenic proteins of AD levels are associated with OH in diabetes mellitus (DM) patients.
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-β (Aβ) and tau.
The neural-derived exosome levels of Aβ42, 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 Aβ42 (β= 0.172, p = 0.018), T-tau (β= 0.159, p = 0.030), and P-T181-tau (β= 0.220, p = 0.003) levels after adjustment for age, sex, APOE ɛ4, duration of type 2 diabetes, HbA1c, and cardiovascular risk factors. Furthermore, the levels of Aβ42, T-tau, and P-T181-tau in neural-derived exosomes were correlated with HIF-1α levels and the drop in mean cerebral blood flow velocity from the supine to upright position.
The presence of OH in DM patients was independently associated with elevated the Aβ42, T-tau, and P-T181-tau levels in neural-derived plasma exosomes. Cerebral hypoperfusion from DM with OH are likely candidate mechanisms.
新出现的证据表明，直立性低血压（OH）在促进阿尔茨海默病（AD）的进展中起作用。血液中的外泌体可以反映大脑的病理变化。
探讨糖尿病（DM）患者中神经源性血浆外泌体 AD 相关致病蛋白水平与 OH 是否相关。
研究共纳入 274 例无痴呆患者：81 例对照组（对照组）、101 例无 OH 的血压正常 DM 患者和 92 例 DM 合并神经源性 OH（DMOH）患者。采用 ELISA 试剂盒检测神经源性外泌体中淀粉样蛋白-β（Aβ）和 tau 水平。
DMOH 组神经源性外泌体 Aβ42、总 tau（T-tau）和 tau 磷酸化 threonine 181（P-T181-tau）水平高于 DM 组和对照组。多变量线性回归分析显示，DM 患者存在 OH 与外泌体 Aβ42（β=0.172，p=0.018）、T-tau（β=0.159，p=0.030）和 P-T181-tau（β=0.220，p=0.003）水平升高相关，调整年龄、性别、APOE ε4、2 型糖尿病病程、糖化血红蛋白和心血管危险因素后。此外，神经源性外泌体中 Aβ42、T-tau 和 P-T181-tau 水平与 HIF-1α水平和从仰卧位到直立位的平均脑血流速度下降相关。
DM 患者存在 OH 与神经源性血浆外泌体中 Aβ42、T-tau 和 P-T181-tau 水平升高独立相关。DM 合并 OH 时的脑灌注不足可能是候选机制。
