Translational potential of synaptic alterations in Alzheimer’s disease patients and amyloid precursor protein knock-in mice

作者：Dina Medina‐Vera, Daniela Enache, Simone Tambaro, Ethar Abuhashish, Cristina Rosell‐Valle, Bengt Winblad, Fernando Rodrı́guez de Fonseca, Erika Bereczki, Per Nilsson · 发表于：Brain Communications · 年份：2022 · DOI：10.1093/braincomms/fcad001 · 被引用次数：4 · 研究领域：Alzheimer's disease research and treatments、Neuroscience and Neuropharmacology Research、Trace Elements in Health

Abstract Synaptic dysfunction is an early event in Alzheimer’s disease. Post-mortem studies suggest that alterations in synaptic proteins are associated with cognitive decline in Alzheimer’s disease. We measured the concentration of three synaptic proteins, zinc transporter protein 3, dynamin1 and AMPA glutamate receptor 3 in cerebrospinal fluid of subjects with mild cognitive impairment (n = 18) and Alzheimer’s disease (n = 18) and compared the levels to cognitively and neurologically healthy controls (n = 18) by using ELISA assay. In addition, we aimed to assess the translational potential of these synaptic proteins in two established amyloid precursor protein knock-in Alzheimer’s disease mouse models by assessing the cerebrospinal fluid, hippocampal and cortical synaptic protein concentrations. Using ELISA, we measured in parallel these three proteins in cerebrospinal fluid and/or brain of 12- and 24-month-old AppNL-F and AppNL-G-F knock-in mice and AppWt control mice. The regional distribution and expression of these proteins were explored upon aging of the App knock-in models by quantitative immunofluorescence microscopy. Notably, we found a significant increase in concentrations of zinc transporter protein 3 and AMPA glutamate receptor 3 in cerebrospinal fluid of both patient groups compared with cognitively healthy controls. Dynamin1 concentration was significantly higher in Alzheimer’s disease patients. Remarkably, patients with mild cognitive impairment who converted...