Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Alzheimers Dement. 2021 May;17(5):788-800. doi: 10.1002/alz.12245. Epub 2021 Mar 4.
The association between cerebral amyloid-β accumulation and downstream CSF biomarkers is not fully understood, particularly in asymptomatic stages.
In 318 cognitively unimpaired participants, we assessed the association between amyloid-β PET (Centiloid), and cerebrospinal fluid (CSF) biomarkers of several pathophysiological pathways. Interactions by Alzheimer's disease risk factors (age, sex and APOE-ε4), and the mediation effect of tau and neurodegeneration were also investigated.
Centiloids were positively associated with CSF biomarkers of tau pathology (p-tau), neurodegeneration (t-tau, NfL), synaptic dysfunction (neurogranin) and neuroinflammation (YKL-40, GFAP, sTREM2), presenting interactions with age (p-tau, t-tau, neurogranin) and sex (sTREM2, NfL). Most of these associations were mediated by p-tau, except for NfL. The interaction between sex and amyloid-β on sTREM2 and NfL was also tau-independent.
Early amyloid-β accumulation has a tau-independent effect on neurodegeneration and a tau-dependent effect on neuroinflammation. Besides, sex has a modifier effect on these associations independent of tau.
脑淀粉样蛋白-β （amyloid-β） 沉积与下游脑脊液 （CSF） 生物标志物之间的关联尚未完全阐明，特别是在无症状阶段。
在 318 名认知正常的参与者中，我们评估了淀粉样蛋白-β PET （Centiloid）与几种病理生理途径的 CSF 生物标志物之间的关联。还研究了阿尔茨海默病风险因素 （年龄、性别和 APOE-ε4） 的相互作用，以及 tau 和神经退行性变的中介效应。
Centiloid 与 tau 病理学 （p-tau）、神经退行性变 （t-tau、NfL）、突触功能障碍 （神经颗粒蛋白） 和神经炎症 （YKL-40、GFAP、sTREM2） 的 CSF 生物标志物呈正相关，与年龄 （p-tau、t-tau、神经颗粒蛋白） 和性别 （sTREM2、NfL） 存在相互作用。除了 NfL 之外，这些关联中的大多数都由 p-tau 介导，而不是 tau。淀粉样蛋白-β 和性别对 sTREM2 和 NfL 的相互作用也与 tau 无关。
早期淀粉样蛋白-β 积累对神经退行性变有 tau 独立的影响，对神经炎症有 tau 依赖的影响。此外，性别对这些关联具有独立于 tau 的修饰作用。
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