Alzheimer's disease biomarker profiling in a memory clinic cohort without common comorbidities.
Alzheimer's disease biomarker profiling in a memory clinic cohort without common comorbidities.
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DOI：
10.1093/braincomms/fcad228
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发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
阿尔茨海默病是一种多因素的疾病，具有很大的异质性。已知合并症如高血压、高胆固醇血症和糖尿病是疾病进展的促成因素。然而，很少有人知道他们的机制，阿尔茨海默氏症的病理和神经退行性变的贡献。本研究的目的是调查与阿尔茨海默病风险机制相关的几种生物标志物与无常见合并症的记忆诊所人群中已确立的阿尔茨海默病标志物之间的关系。我们研究了13种分子标记物，这些标记物代表了记忆诊所患者脑脊液中阿尔茨海默病发病机制的关键机制，这些患者未被诊断为高血压、高胆固醇血症或糖尿病，也未被诊断为其他神经退行性疾病。使用协方差分析比较临床组之间的生物标志物水平。通过线性回归分析关联。两步聚类分析用于确定患者聚类。两个关键的标志物进行了分析，通过免疫荧光染色在非痴呆症的控制和阿尔茨海默氏症的个人海马。本研究共纳入90例受试者的CSF样本：30例主观认知下降患者（年龄62.4 ± 4.38，女性60%），30例轻度认知障碍患者（年龄65.6 ± 7.48，女性50%）和30例阿尔茨海默病患者（年龄68.2 ± 7.86，女性50%）。血管紧张素原、硫氧还蛋白-1和白细胞介素-15与阿尔茨海默病病理学、突触和轴突损伤标志物的相关性最显著。在轻度认知障碍和阿尔茨海默病患者中，突触体相关蛋白25 kDa和神经丝轻链增加。通过生物学功能筛选的生物标志物显示，炎症和存活成分与阿尔茨海默病病理、突触功能障碍和轴突损伤相关。此外，血管/代谢成分与突触功能障碍有关。在数据驱动的分析中，确定了两个患者群：与群2相比，群1具有增加的氧化应激、血管病理学和神经炎症的CSF标志物，并且以升高的突触和轴突损伤为特征。临床组在聚类之间均匀分布。对死后海马组织的分析表明，与非痴呆对照组相比，阿尔茨海默病患者的血管紧张素原染色更高，并与磷酸化tau蛋白共定位。认知障碍患者中生物标志物驱动的内表型的鉴定进一步突出了阿尔茨海默病的生物异质性以及定制预防和治疗策略的重要性。Daniilidou等人表明，与阿尔茨海默病风险机制相关的几种生物标志物与无常见合并症的记忆诊所人群中已确立的阿尔茨海默病标志物相关。他们进一步定义了两个生物学上不同的患者群，这些患者群可能受到导致痴呆的不同机制的影响。
Alzheimer’s disease is a multifactorial disorder with large heterogeneity. Comorbidities such as hypertension, hypercholesterolaemia and diabetes are known contributors to disease progression. However, less is known about their mechanistic contribution to Alzheimer’s pathology and neurodegeneration. The aim of this study was to investigate the relationship of several biomarkers related to risk mechanisms in Alzheimer’s disease with the well-established Alzheimer’s disease markers in a memory clinic population without common comorbidities. We investigated 13 molecular markers representing key mechanisms underlying Alzheimer’s disease pathogenesis in CSF from memory clinic patients without diagnosed hypertension, hypercholesterolaemia or diabetes nor other neurodegenerative disorders. An analysis of covariance was used to compare biomarker levels between clinical groups. Associations were analysed by linear regression. Two-step cluster analysis was used to determine patient clusters. Two key markers were analysed by immunofluorescence staining in the hippocampus of non-demented control and Alzheimer’s disease individuals. CSF samples from a total of 90 participants were included in this study: 30 from patients with subjective cognitive decline (age 62.4 ± 4.38, female 60%), 30 with mild cognitive impairment (age 65.6 ± 7.48, female 50%) and 30 with Alzheimer’s disease (age 68.2 ± 7.86, female 50%). Angiotensinogen, thioredoxin-1 and interleukin-15 had the most prominent associations with Alzheimer’s disease pathology, synaptic and axonal damage markers. Synaptosomal-associated protein 25 kDa and neurofilament light chain were increased in mild cognitive impairment and Alzheimer’s disease patients. Grouping biomarkers by biological function showed that inflammatory and survival components were associated with Alzheimer’s disease pathology, synaptic dysfunction and axonal damage. Moreover, a vascular/metabolic component was associated with synaptic dysfunction. In the data-driven analysis, two patient clusters were identified: Cluster 1 had increased CSF markers of oxidative stress, vascular pathology and neuroinflammation and was characterized by elevated synaptic and axonal damage, compared with Cluster 2. Clinical groups were evenly distributed between the clusters. An analysis of post-mortem hippocampal tissue showed that compared with non-demented controls, angiotensinogen staining was higher in Alzheimer’s disease and co-localized with phosphorylated-tau. The identification of biomarker-driven endophenotypes in cognitive disorder patients further highlights the biological heterogeneity of Alzheimer’s disease and the importance of tailored prevention and treatment strategies. Daniilidou et al. showed that several biomarkers related to risk mechanisms in Alzheimer’s disease are associated with the well-established Alzheimer’s disease markers in a memory clinic population without common comorbidities. They further defined two biologically distinct patient clusters that are likely affected by different mechanisms leading to dementia.
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影响因子：
5.6
作者：
Loera-Valencia R;Eroli F;Garcia-Ptacek S;Maioli S
通讯作者：
Maioli S
脑和认知脆弱的相交的脑肾素 - 血管紧张素系统。
影响因子：
4.3
作者：
Cosarderelioglu C;Nidadavolu LS;George CJ;Oh ES;Bennett DA;Walston JD;Abadir PM
通讯作者：
Abadir PM
DOI：
10.1186/s13195-018-0339-1
发表时间：
2018-01-23
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Gaetani L;Höglund K;Parnetti L;Pujol-Calderon F;Becker B;Eusebi P;Sarchielli P;Calabresi P;Di Filippo M;Zetterberg H;Blennow K
通讯作者：
Blennow K
影响因子：
48
作者：
Kellar, Derek;Craft, Suzanne
通讯作者：
Craft, Suzanne
影响因子：
7.4
作者：
Griffiths, William J.;Abdel-Khalik, Jonas;Wang, Yuqin
通讯作者：
Wang, Yuqin