Linking human cerebral and ocular waste clearance: Insights from tear fluid and ultra-high field MRI

IF 5.1 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2024-11-08 DOI:10.1016/j.nbd.2024.106730

Merel M. van der Thiel , Nienke van de Sande , Anouk Meeusen , Gerhard S. Drenthen , Alida A. Postma , Rudy M.M.A. Nuijts , Noa van der Knaap , Inez H.G.B. Ramakers , Carroll A.B. Webers , Walter H. Backes , Marlies Gijs , Jacobus F.A. Jansen

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Abstract

Impaired cerebral waste clearance (i.e., glymphatics) is evident in aging and neurodegenerative disorders, such as Alzheimer's disease, where an impaired waste clearance system could be related to the accumulation of pathological proteins (e.g., tau). One marker of impaired cerebral clearance is the abundance of enlarged perivascular spaces (PVS). Preclinical studies propose a similar clearance system in the eye, driven by intraocular pressure (IOP). This cross-sectional pilot study explores the link between ocular and cerebral waste clearance by examining the association between MRI-visible PVS, tear fluid total-tau, and IOP.

Thirty cognitively healthy participants, all aged over 55 years, underwent 7 Tesla MRI, with PVS visually rated in the centrum semiovale (CSO) and basal ganglia. Tear fluid was collected using paper Schirmer's strips and analyzed for total-tau using enzyme-linked immunosorbent assay. IOP was measured using non-contact tonometry. Partial Spearman's correlation coefficients of eye and brain markers were calculated, adjusted for age, sex, tear fluid-wetting length, and hemispheric region of interest volume.

Higher CSO PVS scores in the left and right hemisphere were associated with higher levels of tear fluid total-tau. Higher CSO PVS scores in both hemispheres were related to lower ipsilateral IOP. The exploratory results suggest that higher tear fluid total-tau and a reduced driving force of ocular waste clearance are connected to impaired cerebral waste clearance in cognitive healthy individuals. This study connects the potential ocular glymphatic system to the cerebral waste clearance system. Clarifying waste clearance biology and validating eye biomarkers for cerebral waste clearance could provide treatment targets and diagnostic opportunities for neurological diseases.

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将人类大脑和眼部废物清除联系起来：泪液和超高磁场核磁共振成像的启示。

在衰老和神经退行性疾病（如阿尔茨海默病）中，大脑废物清除（即glymphatics）功能受损是显而易见的，废物清除系统受损可能与病理蛋白（如tau）的积累有关。脑清除功能受损的一个标志是血管周围空隙（PVS）大量扩大。临床前研究提出，眼内压（IOP）也会驱动类似的清除系统。这项横断面试验性研究通过检查核磁共振成像可见血管周围间隙、泪液总陶和眼压之间的关联，探索眼部和大脑废物清除之间的联系。30 名认知健康的参与者（年龄均超过 55 岁）接受了 7 T 磁共振成像检查，并对半脑中心（CSO）和基底节的 PVS 进行了目测评级。使用纸质施尔默试纸收集泪液，并使用酶联免疫吸附法分析总 tau。使用非接触式眼压计测量眼压。计算了眼睛和大脑标记物的部分斯皮尔曼相关系数，并对年龄、性别、泪液湿润长度和半球感兴趣区体积进行了调整。左半球和右半球较高的 CSO PVS 分数与较高的泪液总 tau 水平相关。两个半球的 CSO PVS 分数越高，同侧眼压越低。探索性结果表明，在认知健康的个体中，较高的泪液总tau和眼部废物清除驱动力的降低与大脑废物清除受损有关。这项研究将潜在的眼部甘液系统与大脑废物清除联系起来。阐明废物清除生物学原理并验证眼部生物标记物对大脑废物清除的作用，可为神经系统疾病提供治疗目标和诊断机会。

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.