Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Department of Neurology, Skåne University Hospital, Lund University, Lund, Sweden.
EMBO Mol Med. 2021 Jun 7;13(6):e14022. doi: 10.15252/emmm.202114022. Epub 2021 May 5.
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.
阿尔茨海默病的特征是β-淀粉样斑块和tau 缠结。磷酸化 tau217（P-tau217）的血浆水平可以准确地区分阿尔茨海默病痴呆与其他痴呆，但尚不清楚这在多大程度上反映了β-淀粉样斑块的积累、tau 缠结的积累，或者两者兼而有之。在一个具有死后神经病理学数据的队列中（N=88），斑块和缠结密度都独立地导致 P-tau217 升高，但在非阿尔茨海默病 tau 病患者（N=9）中 P-tau217 没有升高。在另一个具有 PET 成像的队列（“BioFINDER-2”，N=426）中复制了几项发现，其中β-淀粉样蛋白和 tau PET 与 P-tau217 独立相关。在疾病早期阶段，P-tau217 浓度与β-淀粉样蛋白 PET（而非 tau PET）相关，而在疾病晚期阶段，与β-淀粉样蛋白和（更强烈）tau PET 相关。最后，P-tau217 在两个队列中介导了β-淀粉样蛋白和 tau 之间的关联，尤其是在外侧颞叶以外的 tau。这些发现支持了这样的假设，即血浆 P-tau217 浓度既受β-淀粉样斑块又受 tau 缠结的影响，并且与 P-tau 参与β-淀粉样蛋白依赖性新皮质 tau 缠结形成的假设相一致。
