Multifactorial pathological processes of Alzheimer’s disease (AD) begin decades prior to clinical onset. Early identification of patients at risk of developing AD using biomarkers reflecting various aspects of pathogenesis is necessary for prevention and early intervention. Cortical β-amyloid (Aβ) burden assessed by positron emission tomography (PET) or cerebrospinal fluid (CSF) levels of Aβ42 are validated biomarkers for early identification. Recently, alterations in levels of neuronal proteins, neuronal pentraxin receptor (NPTXR) and neurofilament light (NfL), in the CSF have emerged as promising AD biomarkers. However, their association with Aβ deposition is not well understood. In this pilot study, we evaluate whether CSF NfL and NPTXR are associated with PET-Aβ imaging and core CSF biomarkers (Aβ42, T-tau, and P-tau). CSF samples were collected from a sub-cohort of participants from the Australian Imaging Biomarkers and Lifestyle study of aging (AIBL) and categorized as either PET-Aβ positive (n = 15) or negative (n = 15). NPTXR was significantly lower in PET-Aβ positive than negative individuals (p = 0.04), and correlated with Aβ42 (rho = 0.69, p < 0.0001), T-tau (rho = 0.45, p = 0.01), and P-tau (rho = 0.51, p = 0.004). However, CSF NfL was not significantly different between PET-Aβ positive and negative individuals and did not correlate with any of the core CSF biomarkers. Similar associations of NPTXR and the core CSF biomarkers persisted in the cognitively normal individuals. Together, NPTXR concentration in CSF may be more sensitive NfL to identify AD risk during the preclinical stage, warranting further investigation into its contribution to AD pathogenesis.

阿尔茨海默氏病（AD）的多因素病理过程在临床发作之前就开始了。为了预防和及早介入，必须使用反映病因各方面的生物标记物及早发现有发展为AD风险的患者。通过正电子发射断层扫描（PET）或脑脊液（CSF）的Aβ42水平评估的皮质β淀粉样蛋白（Aβ）负担是经过验证的生物标志物，可用于早期识别。最近，脑脊液中神经元蛋白，神经元五种毒素受体（NPTXR）和神经丝轻（NfL）的水平变化已成为有前途的AD生物标志物。然而，它们与Aβ沉积的关联尚不十分清楚。在这项初步研究中，我们评估CSF NfL和NPTXR是否与PET-Aβ成像和核心CSF生物标志物（Aβ42，T-tau和P-tau）相关。CSF样本来自澳大利亚成像生物标志物和生活方式老化研究（AIBL）的一个参与者亚组，分类为PET-Aβ阳性（n = 15）或阴性（n = 15）。PET-Aβ阳性患者的NPTXR显着低于阴性患者（p  = 0.04），并与Aβ42（rho = 0.69，p  <0.0001），T-tau（rho = 0.45，p  = 0.01）和P-tau（rho = 0.51，p  = 0.004）相关。但是，PET-Aβ阳性和阴性个体之间的CSF NfL没有显着差异，并且与任何核心CSF生物标记物均不相关。在认知正常的个体中，NPTXR和核心CSF生物标志物的相似关联仍然存在。总之，脑脊液中的NPTXR浓度在临床前阶段可能更敏感NfL来识别AD风险，因此有必要进一步研究其对AD发病机理的作用。