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阿尔茨海默病和行为变异型额颞叶痴呆中脑脊液生物标志物与灰质萎缩的相关性

Correlations between Cerebrospinal Fluid Biomarkers and Gray Matter Atrophy in Alzheimer's and Behavioural Variant Frontotemporal Dementia.

作者信息

Scianatico Gaetano, Manippa Valerio, Zaca Domenico, Jovicich Jorge, Tafuri Benedetta, Rivolta Davide, Logroscino Giancarlo

机构信息

Department of Education, Psychology and Communication, University of Bari Aldo Moro, 70121, Bari, Italy.

Center for Neurodegenerative Diseases and the Aging Brain, University of Bari Aldo Moro at Pia Fondazione "Cardinale G. Panico", 73039, Tricase, Lecce, Italy.

出版信息

Curr Alzheimer Res. 2024;21(6):371-383. doi: 10.2174/0115672050330903240919074725.

Abstract

INTRODUCTION

Distinguishing between frontotemporal dementia (FTD) and Alzheimer's disease (AD) in their early stages remains a significant clinical challenge. Cerebrospinal fluid (CSF) biomarkers (total Tau, phosphorylated Tau, and beta-amyloid) are promising candidates for identifying early differences between these conditions. This study investigates the relationship between grey matter density and CSF markers in the behavioural variant of frontotemporal dementia (bvFTD) and Alzheimer's disease (AD).

METHOD

CSF and 3D T1-weighted magnetic resonance (MR) images were acquired from 14 bvFTD patients, 15 AD patients, and 13 cognitively normal (CN) matched subjects. The CSF markers and their relative ratios (total Tau/beta-amyloid, phosphorylated Tau/beta-amyloid) were compared across the three groups. Voxel-based morphometry (VBM) was performed to characterize the anatomical changes in bvFTD and AD patients compared to CN subjects. Grey matter density maps were obtained by automatic segmentation of 3.0 Tesla 3D T1-Weighted MR Images, and their correlation with CSF markers and relative ratios was investigated.

RESULTS

Results demonstrated that, as compared to CN subjects, AD patients are characterised by higher CSF total Tau levels and lower beta-amyloid levels; however, beta-amyloid and relative ratios discriminated AD from bvFTD. In addition, AD and bvFTD patients showed different patterns of atrophy, with AD exhibiting more central (temporal areas) and bvFTD more anterior (frontal areas) atrophy. A correlation was found between grey matter density maps and CSF marker concentrations in the AD group, with total Tau and phosphorylated Tau levels showing a high association with low grey matter density in the left superior temporal gyrus.

CONCLUSION

Overall, while bvFTD lacks a CSF marker profile, CSF beta-amyloid levels are useful for differentiating AD from bvFTD. Furthermore, MR structural imaging can contribute significantly to distinguishing between the two pathologies.

摘要

引言

在早期阶段区分额颞叶痴呆(FTD)和阿尔茨海默病(AD)仍然是一项重大的临床挑战。脑脊液(CSF)生物标志物(总 Tau 蛋白、磷酸化 Tau 蛋白和β-淀粉样蛋白)有望用于识别这两种疾病的早期差异。本研究调查了行为变异型额颞叶痴呆(bvFTD)和阿尔茨海默病(AD)中灰质密度与脑脊液标志物之间的关系。

方法

从 14 例 bvFTD 患者、15 例 AD 患者和 13 例认知正常(CN)的匹配受试者中获取脑脊液和三维 T1 加权磁共振(MR)图像。比较三组患者的脑脊液标志物及其相对比值(总 Tau 蛋白/β-淀粉样蛋白、磷酸化 Tau 蛋白/β-淀粉样蛋白)。采用基于体素的形态学测量(VBM)来描述 bvFTD 和 AD 患者与 CN 受试者相比的解剖学变化。通过对 3.0 特斯拉三维 T1 加权 MR 图像进行自动分割获得灰质密度图,并研究其与脑脊液标志物及相对比值的相关性。

结果

结果表明,与 CN 受试者相比,AD 患者的脑脊液总 Tau 蛋白水平较高,β-淀粉样蛋白水平较低;然而,β-淀粉样蛋白及其相对比值可区分 AD 和 bvFTD。此外,AD 和 bvFTD 患者表现出不同的萎缩模式,AD 表现为更集中于中部(颞叶区域)萎缩,bvFTD 则更多为前部(额叶区域)萎缩。在 AD 组中发现灰质密度图与脑脊液标志物浓度之间存在相关性,总 Tau 蛋白和磷酸化 Tau 蛋白水平与左侧颞上回低灰质密度高度相关。

结论

总体而言,虽然 bvFTD 缺乏脑脊液标志物特征,但脑脊液β-淀粉样蛋白水平有助于区分 AD 和 bvFTD。此外,MR 结构成像对区分这两种病理状态有显著贡献。

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