We investigated the biomarker profile of neurodegeneration, Alzheimer’s and Lewy body pathology in the CSF of 148 polysomnography-confirmed patients with isolated REM sleep behavior disorder (IRBD), a condition that precedes Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). We assessed misfolded α-synuclein (AS) by RT-QuIC assay, amyloid-beta peptides (Aβ₄₂ and Aβ₄₀), phosphorylated tau (p-tau), and total tau (t-tau) by CLEIA and neurofilament light chain (NfL) by ELISA. We detected AS in 75.3% of patients, pathologically decreased Aβ₄₂/Aβ₄₀ ratio in 22.5%, increased p-tau in 15.5%, increased t-tau in 14.9%, and elevated NfL in 14.7%. After a mean follow-up of 2.48 ± 2.75 years, 47 (38.1%) patients developed PD (n = 24) or DLB (n = 23). At CSF collection, AS positivity [HR 4.05 (1.26–12.99), p = 0.019], mild cognitive impairment [3.86 (1.96–7.61), p < 0.001], and abnormal DAT-SPECT [2.31 (1.09–4.91), p < 0.030] were independent predictors of conversion to PD and DLB. Among the other CSF markers, only elevated p-tau/Aβ₄₂ was predictive of conversion, although only to DLB and not as an independent variable. In IRBD, CSF AS assessment by RT-QuIC provides an added value in defining the risk of short-term conversion to PD and DLB independent of clinical and instrumental investigations. Positive Alzheimer's disease (AD) pathology markers and elevated NfL occur in a subgroup of patients, but p-tau/Aβ₄₂ is the only marker that predicts short-term conversion to DLB. Longer follow-up is needed to assess if AD biomarkers predict the later development of PD and DLB in IRBD.

我们调查了 148 名多导睡眠图确诊患有孤立性快速眼动睡眠行为障碍 (IRBD) 患者脑脊液中神经退行性、阿尔茨海默病和路易体病理学的生物标志物谱，IRBD 是帕金森病 (PD) 和路易体痴呆 (DLB) 之前的疾病。我们通过 RT-QuIC 检测评估了错误折叠的 α-突触核蛋白 (AS)，通过 CLEIA 和神经丝轻链评估了淀粉样蛋白-β 肽（Aβ ₄₂和 Aβ ₄₀ ）、磷酸化 tau (p-tau) 和总 tau (t-tau)（ NfL) 通过 ELISA。我们在 75.3% 的患者中检测到 AS，22.5% 的患者病理学上 Aβ ₄₂ /Aβ ₄₀比率降低，15.5% 的 p-tau 升高，14.9% 的 t-tau 升高，14.7% 的 NfL 升高。平均随访 2.48 ± 2.75 年后，47 名 (38.1%) 患者出现 PD ( n = 24) 或 DLB ( n = 23)。脑脊液采集时，AS 阳性 [HR 4.05 (1.26–12.99)， p = 0.019]，轻度认知障碍 [3.86 (1.96–7.61)， p < 0.001]，以及异常 DAT-SPECT [2.31 (1.09–4.91)， p < 0.030] 是转化为 PD 和 DLB 的独立预测因子。在其他 CSF 标志物中，只有升高的 p-tau/Aβ ₄₂可以预测转化，尽管只是转化为 DLB，而不是作为自变量。在 IRBD 中，RT-QuIC 进行的 CSF AS 评估在定义独立于临床和仪器研究的短期转化为 PD 和 DLB 的风险方面提供了附加值。部分患者出现阿尔茨海默病 (AD) 病理标志物阳性和 NfL 升高，但 p-tau/Aβ ₄₂是预测短期转为 DLB 的唯一标志物。需要更长时间的随访来评估 AD 生物标志物是否可以预测 IRBD 中 PD 和 DLB 的后期发展。