研究:血管损伤可能是老年痴呆症的司机
![Loss of retinal endothelial claudin-5 in MCI and AD patients in relation to retinal vascular amyloidosis, CAA, and cognitive deficit. A, Representative images of immunofluorescent staining for claudin-5 (red), collagen IV (ColIV, green), and DAPI (blue) on post mortem cross-sections of retina from CN (n = 21 [control]) patients as well as from patients with MCI (n = 10) and those with AD (n = 21) with different degrees of CAA severity scores. All scale bars = 20 µm. B,C, Quantitative analysis of retinal vascular claudin-5 IR separately in capillaries and LBVs from all experimental groups stratified by (B) CAA severity scores and by (C) diagnostic groups (n = 53 in total). D, Average of retinal vascular claudin-5 IR in capillaries and LBVs stratified by sex in the same cohort (n = 53 total). E, Pearson's coefficient (r) correlation between CAA severity scores and claudin-5 in retinal capillaries (red) and LBVs (gray) (n = 35 total). F, Heatmaps illustrating Pearson's correlations between retinal claudin-5 in capillaries and LBVs versus brain pathology and cognitive decline, including Aβ plaques (Aβ-P), NFTs, NTs, ATR, MMSE scores, CDR scores, CAA severity scores, Braak stages, and A (amyloid) B (Braak) C (Consortium to Establish a Registry for Alzheimer's Disease) average scores in AD (n = 18), MCI (n = 10), and CN (n = 9) human donors (n = 37 total). Pseudo-color red and numbers demonstrate the strength of (r) correlation power; statistical significance is demonstrated as follows: n.s., not significant, *P < 0.05, **P < 0.01, ****P < 0.0001. G,H, Pearson's coefficient (r) correlation between (G) retinal Aβ40 versus claudin-5 in capillaries and (H) retinal arteriolar Aβ40 versus claudin-5 in LBVs. Data from individual donors (circles) as well as group means ± standard error of the mean are shown. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, by one-way analysis of variance with Tukey's post hoc multiple comparison test. Two-group statistical analysis was performed using an unpaired two-tailed Student t test, and results are shown in parentheses. Percentage decreases are shown in red. Aβ, amyloid beta; AD, Alzheimer's disease; ATR, atrophy; B, Black; C, Caucasian (White); CAA, cerebral amyloid angiopathy; CDR, Clinical Dementia Rating; CN, cognitively normal; F, female; H, Hispanic; IR, immunoreactivity; LBVs, large blood vessels; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; NFTs, neurofibrillary tangles; NTs, neutrophil threads; yrs, years old. Credit: Alzheimer's & Dementia (2023). DOI: 10.1002/alz.13086 研究:血管损伤可能是老年痴呆症的司机](https://scx1.b-cdn.net/csz/news/800a/2023/study-blood-vessel-dam.jpg)
血管畸形的眼睛是一个主要因素在阿尔茨海默病的发展,据研究从西奈研究人员发表在《华尔街日报》阿尔茨海默氏症和老年痴呆症。这些变化对应于大脑的变化,为早期诊断提供一种新的可能性。
“这项研究提供了一个新的认识与阿尔茨海默病相关的血管变化,特别是视网膜神经组织的层后面的眼睛,“玛雅Koronyo-Hamaoui说,博士,神经学、神经外科和生物医学科学在cedars - sinai教授和这项研究的资深作者。“这还指出,阿尔茨海默病导致的损害的血管在视网膜上,使一个新的、非侵入性的途径早期诊断和监测疾病进展。”
调查人员而收集的视网膜血管24人捐助者与阿尔茨海默病,10捐助者轻度认知障碍27与正常认知。
阿尔茨海默病和轻度认知障碍患者,他们发现阿尔茨海默病的早期症状之一日期:血视网膜屏障的破坏,严格防止加入细胞有害物质进入视网膜组织。
“在老年痴呆症患者,我们发现有一个赤字高达70%的障碍,这意味着有害物质可以通过,进入视网膜组织,“Haoshen Shi说,医学博士,博士项目科学家、该研究的第一作者。“我们看到这个发生早期,患者只有轻度功能障碍。”
血视网膜屏障损伤是密切相关的条件脑淀粉样血管病(CAA) - - -淀粉样蛋白的积累小血管——其他脑部血管疾病。
“目前,检测CAA患者的唯一方法就是在死后大脑组织样本,“Koronyo-Hamaoui说。”进一步的研究和开发先进的视网膜成像、血管和blood-retinal屏障损伤可以给我们一个机会来检测CAA患者生活。”
研究还发现,存款的一种叫做β淀粉样蛋白的蛋白质40积累在阿尔茨海默氏症患者的视网膜动脉,动脉僵硬,扰乱血液流动和防止动脉清除视网膜的有害物质。进一步的研究是必要的,以确定的存款因血管损伤积累,或者实际造成的损害,Koronyo-Hamaoui说。
“视网膜和大脑组织富含血管,和高血液供应是基本功能,“Koronyo-Hamaoui说。“血液供应的限制,可能会出现由于损害我们展示发生在这里,意味着这些细胞没有得到他们所需要的氧气和营养。”
先进的视网膜成像,观察血管和蛋白质积累生活的无创患者,在发展,但还没有得到美国食品和药物管理局批准,Koronyo-Hamaoui说。
”作为解剖大脑的扩展,视网膜已经广泛研究了作为一个窗口,中枢神经系统疾病,”基斯说l .黑色,医学博士,神经外科系主任和露丝和劳伦斯·哈维在神经科学在cedars - sinai椅子。“这项工作增加了最新进展在先进的视网膜成像和识别其他视网膜生物标志物促进阿尔茨海默病早期检测的科学。”
同时,Koronyo-Hamaoui建议人们去做他们可以来保持他们的循环系统,包括血管在视网膜和大脑健康,防止CAA和痴呆。
“控制高血压,吃健康的饮食习惯低糖,减少饮酒,避免吸烟可以帮助防止慢性炎症和损伤血管”,Koronyo-Hamaoui说。“我们的研究显示,血管损伤是一个主要的元素在阿尔茨海默氏症的进展。”
更多信息:Haoshen et al,视网膜动脉Aβ40沉积与紧密连接损失和脑淀粉样血管病在MCI和AD患者,阿尔茨海默氏症和老年痴呆症(2023)。DOI: 10.1002 / alz.13086