Plasma Glial Fibrillary Acidic Protein Levels Differ Along the Spectra of Amyloid Burden and Clinical Disease Stage.
Plasma Glial Fibrillary Acidic Protein Levels Differ Along the Spectra of Amyloid Burden and Clinical Disease Stage.
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DOI：
10.3233/jad-200755
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Casaletto KB
中科院分区：
文献类型：
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作者：
Asken BM;Elahi FM;La Joie R;Strom A;Staffaroni AM;Lindbergh CA;Apple AC;You M;Weiner-Light S;Brathaban N;Fernandes N;Karydas A;Wang P;Rojas JC;Boxer AL;Miller BL;Rabinovici GD;Kramer JH;Casaletto KB
测量血浆胶质细胞酸性蛋白（GFAP）和皮质淀粉样蛋白-β（Aβ）可能有助于了解衰老和阿尔茨海默病（AD）中星形胶质细胞的变化。在典型的从衰老到AD痴呆的老年人中，研究血浆GFAP和皮质Aβ沉积之间的相关性。我们研究了来自UCSF的两份独立样本（队列1，N = 50;队列2，N = 37），涵盖了临床严重程度（CDR框总和; CDR-SB）和Aβ-PET负荷谱。使用florbetapir或Pittsburgh化合物B完成Aβ-PET，并将标准化摄取值比率转换为Centiloid（CL）量表进行分析。所有CDR-SB > 0的受试者均为Aβ-PET阳性，而临床正常受试者（CDR-SB = 0）为Aβ-PET阳性和阴性的混合。回归分析评价了血浆GFAP、Aβ-PET和临床严重程度之间的主效应和相互作用。在两个队列中，在临床正常的老年人中，血浆GFAP随Aβ-PET CL线性增加。在队列2中，包括更严重的临床功能障碍和Aβ-PET负荷的参与者，Aβ和GFAP之间的关系呈曲线型（倒U形;二次模型R2变化= 0.165，p = 0.009），Aβ-PET与CDR-SB相互作用（R2变化= 0.164，p = 0.007）：中度功能障碍老年人（CDR-SB = 0.5-4.0）显示弱的免疫应答。Aβ-PET CL与血浆GFAP之间存在（负）相关性，而老年痴呆患者（CDR-SB > 4.0）显示较高的Aβ-PET CL与较低的血浆GFAP具有强的负相关性。星形胶质细胞完整性和皮质Aβ之间的关系可能是高度动态的，在疾病早期具有线性正相关，在更严重的疾病阶段有所不同。
Measuring plasma glial fibrillary acidic protein (GFAP) alongside cortical amyloid-β (Aβ) may shed light on astrocytic changes in aging and Alzheimer’s disease (AD). To examine associations between plasma GFAP and cortical Aβ deposition in older adults across the typical aging-to-AD dementia spectrum. We studied two independent samples from UCSF (Cohort 1, N = 50; Cohort 2, N = 37) covering the spectra of clinical severity (CDR Sum of Boxes; CDR-SB) and Aβ-PET burden. Aβ-PET was completed with either florbetapir or Pittsburgh Compound B and standardized uptake value ratios were converted to the Centiloid (CL) scale for analyses. All participants with CDR-SB > 0 were Aβ-PET positive, while clinically normal participants (CDR-SB = 0) were a mix of Aβ-PET positive and negative. Regression analyses evaluated main effect and interaction associations between plasma GFAP, Aβ-PET, and clinical severity. In both cohorts, plasma GFAP increased linearly with Aβ-PET CLs in clinically normal older adults. In Cohort 2, which included participants with more severe clinical dysfunction and Aβ-PET burden, the association between Aβ and GFAP became curvilinear (inverted U-shape; quadratic model R2 change = 0.165, p = 0.009), and Aβ-PET interacted with CDR-SB (R2 change = 0.164, p = 0.007): older adults with intermediate functional impairment (CDR-SB = 0.5–4.0) showed a weak (negative) association between Aβ-PET CLs and plasma GFAP, while older adults with dementia (CDR-SB > 4.0) showed a strong, negative association of higher Aβ-PET CLs with lower plasma GFAP. The relationship between astrocytic integrity and cortical Aβ may be highly dynamic, with linear, positive associations early in disease that diverge in more severe disease stages.