Klafki Hans-Wolfgang, Wirths Oliver, Mollenhauer Brit, Liepold Thomas, Rieper Petra, Esselmann Hermann, Vogelgsang Jonathan, Wiltfang Jens, Jahn Olaf
Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August-University, Goettingen, Germany.
Department of Neurology, University Medical Center Goettingen (UMG), Georg-August-University, Goettingen, Germany.
J Neurochem. 2022 Mar;160(5):578-589. doi: 10.1111/jnc.15571. Epub 2022 Jan 18.
Neurochemical biomarkers can support the diagnosis of Alzheimer's disease and may facilitate clinical trials. In blood plasma, the ratio of the amyloid-β (Aβ) peptides Aβ-3-40/Aβ1-42 can predict cerebral amyloid-β pathology with high accuracy (Nakamura et al., 2018). Whether or not Aβ-3-40 (aka. amyloid precursor protein (APP) 669-711) is also present in cerebrospinal fluid (CSF) is not clear. Here, we investigated whether Aβ-3-40 can be detected in CSF and to what extent the CSF Aβ-3-40/Aβ42 ratio is able to differentiate between individuals with or without amyloid-β positron emission tomography (PET) evidence of brain amyloid. The occurrence of Aβ-3-40 in human CSF was assessed by immunoprecipitation followed by mass spectrometry. For quantifying the CSF concentrations of Aβ-3-40 in 23 amyloid PET-negative and 17 amyloid PET-positive subjects, we applied a sandwich-type immunoassay. Our findings provide clear evidence of the presence of Aβ-3-40 and Aβ-3-38 in human CSF. While there was no statistically significant difference in the CSF concentration of Aβ-3-40 between the two diagnostic groups, the CSF Aβ-3-40/Aβ42 ratio was increased in the amyloid PET-positive individuals. We conclude that Aβ-3-40 appears to be a regular constituent of CSF and may potentially serve to accentuate the selective decrease in CSF Aβ42 in Alzheimer's disease.
神经化学生物标志物可辅助阿尔茨海默病的诊断，并可能促进临床试验。在血浆中，淀粉样β蛋白（Aβ）肽Aβ-3-40/Aβ1-42的比值能够高精度地预测脑淀粉样β蛋白病变（中村等人，2018年）。目前尚不清楚Aβ-3-40（又名淀粉样前体蛋白（APP）669-711）是否也存在于脑脊液（CSF）中。在此，我们研究了脑脊液中能否检测到Aβ-3-40，以及脑脊液Aβ-3-40/Aβ42比值在区分有无脑淀粉样蛋白正电子发射断层扫描（PET）证据的个体方面的能力。通过免疫沉淀结合质谱法评估人脑脊液中Aβ-3-40的存在情况。为了定量23名淀粉样蛋白PET阴性和17名淀粉样蛋白PET阳性受试者脑脊液中Aβ-3-40的浓度，我们采用了夹心型免疫测定法。我们的研究结果明确证明了人脑脊液中存在Aβ-3-40和Aβ-3-38。虽然两个诊断组之间脑脊液中Aβ-3-40的浓度没有统计学上的显著差异，但淀粉样蛋白PET阳性个体的脑脊液Aβ-3-40/Aβ42比值升高。我们得出结论，Aβ-3-40似乎是脑脊液的一种常规成分，可能有助于突出阿尔茨海默病患者脑脊液中Aβ42的选择性降低。
