Chung, S. Yang, J. Kim, H.J. Hwang, Eun Mi Lee, W. Suh, K. Choi, H. Mook-Jung, I. 2024-01-19T14:03:34Z 2024-01-19T14:03:34Z 2021-09-02 2021-08 0301-0082 https://pubs.kist.re.kr/handle/201004/116670 Amyloid-β (Aβ) and tau are major pathological hallmarks of Alzheimer's disease (AD). Several studies have revealed that Aβ accelerates pathological tau transition and spreading during the disease progression, and that reducing tau can mitigate pathological features of AD. However, molecular links between Aβ and tau pathologies remain elusive. Here, we suggest a novel role for the plexin-A4 as an Aβ receptor that induces aggregated tau pathology. Plexin-A4, previously known as proteins involved in regulating axon guidance and synaptic plasticity, can bound to Aβ with co-receptor, neuropilin-2. Genetic downregulation of plexin-A4 in neurons was sufficient to prevent Aβ-induced activation of CDK5 and reduce tau hyperphosphorylation and aggregation, even in the presence of Aβ. In an AD mouse model that manifests both Aβ and tau pathologies, genetic downregulation of plexin-A4 in the hippocampus reduced tau pathology and ameliorated spatial memory impairment. Collectively, these results indicate that the plexin-A4 is capable of mediating Aβ-induced tau pathology in AD pathogenesis. ？ 2021 The Authors English Elsevier Ltd Plexin-A4 mediates amyloid-β-induced tau pathology in Alzheimer’s disease animal model Article 10.1016/j.pneurobio.2021.102075 1 Progress in Neurobiology, v.203 Progress in Neurobiology 203 Y scie scopus 000661942400002 2-s2.0-85107048669 Neurosciences Neurosciences & Neurology Review AGGREGATION ORIENTATION BLOOD-BRAIN-BARRIER PHOSPHORYLATED TAU STRUCTURAL BASIS SEMAPHORINS RECEPTOR PROTEIN IDENTIFICATION NEUROPILIN-2 Alzheimer&apos s disease Amyloid-β Aβ-Tau axis neuropilin-2 plexin-A4 Tau