Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau.
Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau.
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DOI：
10.15252/emmm.202114022
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发表时间：
2021-06-07
影响因子：
11.1
通讯作者：
Hansson O
中科院分区：
文献类型：
--
作者：
Mattsson-Carlgren N;Janelidze S;Bateman RJ;Smith R;Stomrud E;Serrano GE;Reiman EM;Palmqvist S;Dage JL;Beach TG;Hansson O
阿尔茨海默病的特征在于β-淀粉样蛋白斑块和tau蛋白缠结。血浆磷酸化tau 217（P-tau 217）水平可以准确区分阿尔茨海默病痴呆症和其他痴呆症，但目前还不清楚这在多大程度上反映了β淀粉样蛋白斑块的积累，tau缠结的积累，或两者兼而有之。在具有死后神经病理学数据的队列中（N = 88），斑块和缠结密度均独立地导致较高的P-tau 217，但在非阿尔茨海默病tau蛋白病患者中P-tau 217未升高（N = 9）。在PET成像队列中重复了几个发现（“BioFINDER-2”，N = 426），其中β-淀粉样蛋白和tau PET与P-tau 217独立相关。P-tau 217浓度与疾病早期阶段的β-淀粉样蛋白PET（而不是tau PET）相关，并与疾病晚期阶段的β-淀粉样蛋白和（更强烈）tau PET相关。最后，P-tau 217在两个队列中介导β淀粉样蛋白和tau之间的关联，特别是对于内侧颞叶以外的tau。这些发现支持血浆P-tau 217浓度通过β-淀粉样蛋白斑块和tau缠结增加的假设，并且与P-tau参与新皮质tau缠结的β-淀粉样蛋白依赖性形成的假设一致。磷酸化tau蛋白（包括P-tau 217）的血浆水平在阿尔茨海默病（AD）中升高。本研究使用死后数据和β淀粉样蛋白和tau蛋白的正电子发射断层扫描（PET），探索了与血浆P-tau 217水平升高相关的潜在过程。
Alzheimer’s disease is characterized by β‐amyloid plaques and tau tangles. Plasma levels of phospho‐tau217 (P‐tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β‐amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post‐mortem neuropathological data (N = 88), both plaque and tangle density contributed independently to higher P‐tau217, but P‐tau217 was not elevated in patients with non‐Alzheimer’s disease tauopathies (N = 9). Several findings were replicated in a cohort with PET imaging (“BioFINDER‐2”, N = 426), where β‐amyloid and tau PET were independently associated with P‐tau217. P‐tau217 concentrations correlated with β‐amyloid PET (but not tau PET) in early disease stages and with both β‐amyloid and (more strongly) tau PET in late disease stages. Finally, P‐tau217 mediated the association between β‐amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P‐tau217 concentration is increased by both β‐amyloid plaques and tau tangles and is congruent with the hypothesis that P‐tau is involved in β‐amyloid‐dependent formation of neocortical tau tangles. Plasma levels of phosphorylated tau, including P‐tau217, are elevated in Alzheimer's disease (AD). This study explores the underlying processes associated with the increased levels of plasma P‐tau217, using post‐mortem data and positron emission tomography (PET) of β‐amyloid and tau.