Alzheimer's disease cerebrospinal fluid biomarkers differentiate patients with Creutzfeldt-Jakob disease and autoimmune encephalitis.

Alzheimer's disease cerebrospinal fluid biomarkers differentiate patients with Creutzfeldt-Jakob disease and autoimmune encephalitis.
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阿尔茨海默氏病脑脊液生物标志物与Creutzfeldt-Jakob病和自身免疫性脑炎的患者区分患者。

DOI:
10.1111/ene.15469
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发表时间:
2022-10
影响因子:
5.1
通讯作者:
--
中科院分区:
医学3区
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--
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自身免疫性脑炎 (AE) 是快速进展性痴呆 (RPD) 的潜在可治疗原因,可能类似于克雅氏病 (CJD)。阿尔茨海默病 (AD) 脑脊液 (CSF) 生物标志物可以区分 CJD 和 AD,但区分 CJD 和 AE 的效用尚不清楚。本研究比较了 CJD 和 AE 中的 AD CSF 生物标志物。研究纳入了 2020 年 3 月至 2021 年 4 月在 Mayo Clinic 接受 Roche Elecsys AD CSF 生物标志物检测的疑似或确诊 CJD 以及疑似或确诊 AE 的患者。比较总 tau (t-tau)、磷酸化 181 tau (p-tau) 和淀粉样蛋白 β42 (Aβ42) 水平。 11例克雅氏病病例中,4例经尸检证实;其余的进行了积极的实时震动诱导转换(RT-QuIC)测试。在 8/15 例 AE 中检测到疾病相关自身抗体:LGI1 和 NIF(各 2 例)以及 NMDAR、CASPR2、DPPX 和 IgLON5。 T-tau 在单变量模型中很好地区分了 CJD 和 AE(OR 1.46 每 100pg/mL,CI 1.17-2.11,p <.05,c=0.93)。 91% 的 CJD 病例 T-tau 升高(中位数 >1300,范围 236 - >1300 pg/mL),其中 55% 高于测定测量极限(>1300 pg/mL)。 20% 的 AE 病例中 T-tau 升高(中位数 158,范围 80->1300 pg/mL)。 CJD 中的 T-tau 含量高于 AE。鉴于 Aβ42 和 p-tau 具有可比性,比率差异可能是由克雅氏病中 t-tau 升高所致。这项研究支持 AD 生物标志物测试在 RPD 患者中的作用。克雅氏病的平均脑脊液 t-tau、t-tau/p-tau 比值和 t-tau/Aβ42 比值高于自身免疫性脑炎
Autoimmune encephalitis (AE) is a potentially treatable cause of rapidly progressive dementia (RPD) that may mimic Creutzfeldt-Jakob disease (CJD). Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers may discriminate CJD from AD, but utility in discriminating CJD and AE is unclear. This study compared AD CSF biomarkers in CJD and AE. Patients with probable or definite CJD and probable or definite AE who underwent Roche Elecsys AD CSF biomarker testing at Mayo Clinic from March 2020 through April 2021 were included. Total-tau (t-tau), phosphorylated181 tau (p-tau), and amyloid-β42 (Aβ42) levels were compared. Of 11 CJD cases, 4 were autopsy proven; the rest had positive real-time quaking-induced conversion (RT-QuIC) testing. Disease-associated autoantibodies were detected in 8/15 cases of AE: LGI1 and NIF (2 cases each), and NMDAR, CASPR2, DPPX, and IgLON5. T-tau provided excellent discrimination between CJD and AE in a univariate model (OR 1.46 per 100pg/mL, CI 1.17-2.11, p <.05, c=0.93). T-tau was elevated in 91% of CJD cases (median >1300, range 236 - >1300 pg/mL), of which 55% were above the limit of assay measurement (>1300 pg/mL). T-tau was elevated in 20% of AE cases (median 158, range 80->1300 pg/mL). T-tau was greater in CJD than AE. Given that Aβ42 and p-tau were comparable, the ratio differences were likely driven by elevated t-tau in CJD. This study supports the role for AD biomarker testing in patients with RPD. Creutzfeldt-Jakob disease has greater mean cerebrospinal fluid t-tau, t-tau/p-tau ratio, and t-tau/Aβ42 ratio than autoimmune encephalitis
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