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Spatial decrease of synaptic density in amnestic mild cognitive impairment follows the tau build-up pattern
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2022-07-06 , DOI: 10.1038/s41380-022-01672-x
Greet Vanderlinden 1 , Jenny Ceccarini 1 , Thomas Vande Casteele 2 , Laura Michiels 3, 4, 5 , Robin Lemmens 3, 4, 5 , Eric Triau 6 , Kim Serdons 7 , Jos Tournoy 8, 9 , Michel Koole 1 , Mathieu Vandenbulcke 2, 10 , Koen Van Laere 1, 7
Affiliation  

Next to amyloid and tau, synaptic loss is a key pathological hallmark in Alzheimer’s disease, closely related to cognitive dysfunction and neurodegeneration. Tau is thought to cause synaptic loss, but this has not been experimentally verified in vivo. In a 2-year follow-up study, dual tracer PET-MR was performed in 12 amnestic MCI patients using 18F-MK-6240 for tau and 11C-UCB-J for SV2A as a proxy for synaptic density. Tau already accumulated in the neocortex at baseline with progression in Braak V/VI at follow-up. While synaptic loss was limited to limbic regions at baseline, it followed the specific tau pattern to stage IV/V regions two years later, indicating that tau spread might drive synaptic vulnerability. Moreover, synaptic density changes correlated to changes in cognitive function. This study shows for the first time in vivo that synaptic loss regionally follows tau accumulation after two years, providing a disease-modifying window of opportunity for (combined) tau-targeting therapies.



中文翻译:

遗忘性轻度认知障碍中突触密度的空间降低遵循 tau 积聚模式

除了淀粉样蛋白和 tau 蛋白,突触缺失是阿尔茨海默病的一个关键病理标志,与认知功能障碍和神经变性密切相关。Tau 被认为会导致突触丢失,但这尚未在体内得到实验验证。在一项为期 2 年的随访研究中,对 12 名遗忘性 MCI 患者进行了双示踪剂 PET-MR,使用18 个F-MK-6240 用于 tau 和11 个SV2A 的 C-UCB-J 作为突触密度的代表。Tau 已经在基线时在新皮质中积累,并在后续的 Braak V/VI 中取得进展。虽然基线时突触丢失仅限于边缘区域,但两年后它遵循特定的 tau 模式进入 IV/V 期区域,这表明 tau 扩散可能会导致突触脆弱。此外,突触密度的变化与认知功能的变化相关。这项研究首次在体内表明,两年后 tau 蛋白积累会导致突触丢失,这为(联合)tau 靶向疗法提供了一个改变疾病的机会窗口。

更新日期:2022-07-06
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