Plasma phosphorylated-tau217 is increased in Niemann-Pick disease type C.

IF 4.1 Q1 CLINICAL NEUROLOGY
Brain communications Pub Date : 2024-10-25 eCollection Date: 2024-01-01 DOI:10.1093/braincomms/fcae375
Fernando Gonzalez-Ortiz, Thomas K Karikari, Danielle Taylor-Te Vruchte, Dawn Shepherd, Bjørn-Eivind Kirsebom, Tormod Fladby, Frances Platt, Kaj Blennow
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Abstract

Niemann-Pick disease type C and Alzheimer's disease are distinct neurodegenerative disorders that share the presence of neurofibrillary tangle pathology. In this multicentre study, we measured plasma phosphorylated-tau217 in controls (n = 60), Niemann-Pick disease type C (n = 71) and Alzheimer's disease (n = 30 positive for amyloid and negative for tau in CSF [A+T-] and n = 30 positive for both [A+T+]). Annual Severity Increment Score and Lysotracker measurements were evaluated in the Niemann-Pick disease type C group to estimate the rate of progression and lysosomal enlargement, respectively. In the cross-sectional analysis, plasma phosphorylated-tau217 was increased in Niemann-Pick disease type C compared with controls (2.52 ± 1.93 versus 1.02 ± 0.34 pg/mL, respectively, P < 0.001) and inversely correlated with age at disease onset (R = -0.54, P < 0.001). In the longitudinal analysis, plasma phosphorylated-tau217 was associated with disease progression determined by Annual Severity Increment Score (R = 0.48, P < 0.001) and lysosomal enlargement (R = 0.26, P = 0.004). We found no differences between A+T- Alzheimer's disease and Niemann-Pick disease type C (2.67 ± 1.18 versus 2.52 ± 1. 93 pg/mL, P = 0.31); however, A+T+ Alzheimer's disease had significantly higher levels than Niemann-Pick disease type C (3.26 ± 1.36 versus 2.52 ± 1.93 pg/mL, P = 0.001). Our findings suggest that plasma p-tau217 can increase in brain disorders with isolated tau pathology. Plasma p-tau217 associations with disease progression and severity make it a potential marker in Niemann-Pick disease type C.

C型尼曼-皮克病患者血浆磷酸化-tau217增高。
尼曼-皮克病 C 型和阿尔茨海默病是两种不同的神经退行性疾病,它们都存在神经纤维缠结病理。在这项多中心研究中,我们测量了对照组(n = 60)、尼曼-皮克病 C 型(n = 71)和阿尔茨海默病(n = 30)的血浆磷酸化-tau217(淀粉样蛋白阳性,脑脊液中 tau 阴性 [A+T-] 和两者均阳性 [A+T+] 的人数分别为 30)。对C型尼曼-皮克病组进行了年度严重程度增量评分和溶酶体追踪器测量,以分别估算疾病进展率和溶酶体增大率。在横断面分析中,与对照组相比,C 型尼曼-皮克病患者血浆磷酸化-tau217 增加(分别为 2.52 ± 1.93 和 1.02 ± 0.34 pg/mL,P < 0.001),并与发病年龄成反比(R = -0.54,P < 0.001)。在纵向分析中,血浆磷酸化-tau217与根据年度严重程度增量评分确定的疾病进展(R = 0.48,P < 0.001)和溶酶体增大(R = 0.26,P = 0.004)相关。我们发现 A+T- 阿尔茨海默病与尼曼-皮克病 C 型(2.67 ± 1.18 对 2.52 ± 1.93 pg/mL,P = 0.31)之间没有差异;但是,A+T+ 阿尔茨海默病的水平明显高于尼曼-皮克病 C 型(3.26 ± 1.36 对 2.52 ± 1.93 pg/mL,P = 0.001)。我们的研究结果表明,血浆中的p-tau217可在具有孤立tau病理学的脑部疾病中升高。血浆p-tau217与疾病进展和严重程度的关系使其成为尼曼-皮克病C型的潜在标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
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