Sauer Mathias, Gomes Bárbara Fernandes, Shahrouki Parasto, Lantero-Rodriguez Juan, Montoliu-Gaya Laia, Camporesi Elena, Belbin Olivia, Alcolea Daniel, Kumar Ashish, Sharma Mitu, Singh Sangeeta, Brinkmalm Gunnar, Gobom Johan, Carmona-Iragui María, Schöll Michael, Janelidze Shorena, Deep Gagan, Blennow Kaj, Zetterberg Henrik, Brinkmalm Ann, Lleó Alberto, Fortea Juan, Hansson Oskar, Ashton Nicholas J, Nilsson Johanna
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Sant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau, Sant Antoni Maria Claret, Barcelona, Spain.
Alzheimers Dement. 2025 Jun;21(6):e70241. doi: 10.1002/alz.70241.
Synaptic dysfunction and loss are pathological hallmarks of neurodegenerative diseases. Neuronal pentraxin 2 (NPTX2), a presynaptic protein involved in synaptic plasticity, has been linked to cognitive decline in Alzheimer's disease (AD) and other neurodegenerative disorders.
We developed and validated a novel single molecule array (Simoa) for NPTX2 in cerebrospinal fluid, which was evaluated in two independent cohorts.
CSF NPTX2 concentration was lower (fold change [FC] 0.82, p < 0.01) in AD patients and Down syndrome individuals (FC 0.56, p < 0.001), compared with cognitively unimpaired patients (CU). It was also associated with Mini-Mental State Examination (MMSE) score (β = 2.51, p < 0.001), tau-PET (β = -0.21, p < 0.01), and cortical thickness (β = 0.08, p < 0.001).
We describe the first assay for NPTX2 on the Simoa platform, where we continue to highlight the valuable addition of NPTX2 to routine diagnostics of suspected cognitive impairment in patients as it associates better with cognition than other, more established AD biomarkers.
Novel method validated for measuring CSF NPTX2 on semi-automated Simoa platform. Method validated for use in CSF, where it shows a significant decrease in both AD and DS patients. Associated with cognition, neurofibrillary tangles, and cortical thickness in AD patients. Associations with cognition are shown to be stronger than those of pTau and NFL.
突触功能障碍和丧失是神经退行性疾病的病理标志。神经元五聚体蛋白2（NPTX2）是一种参与突触可塑性的突触前蛋白，与阿尔茨海默病（AD）和其他神经退行性疾病的认知衰退有关。
我们开发并验证了一种用于检测脑脊液中NPTX2的新型单分子阵列（Simoa），并在两个独立队列中进行了评估。
与认知未受损患者（CU）相比，AD患者和唐氏综合征个体的脑脊液NPTX2浓度较低（倍数变化[FC] 0.82，p < 0.01），唐氏综合征个体的浓度更低（FC 0.56，p < 0.001）。它还与简易精神状态检查表（MMSE）评分（β = 2.51，p < 0.001）、tau正电子发射断层扫描（β = -0.21，p < 0.01）和皮质厚度（β = 0.08，p < 0.001）相关。
我们描述了在Simoa平台上首次对NPTX2进行的检测，我们继续强调将NPTX2添加到疑似认知障碍患者的常规诊断中的价值，因为它与认知的关联比其他更成熟的AD生物标志物更好。
在半自动Simoa平台上验证的用于测量脑脊液NPTX2的新方法。该方法在脑脊液检测中得到验证，在AD和DS患者中均显示出显著降低。与AD患者的认知、神经原纤维缠结和皮质厚度相关。与认知的关联比磷酸化tau蛋白（pTau）和神经丝轻链（NFL）更强。
