Network-guided analysis of hippocampal proteome identifies novel proteins that colocalize with A β in a mice model of early-stage Alzheimer's disease.

Network-guided analysis of hippocampal proteome identifies novel proteins that colocalize with Aβ in a mice model of early-stage Alzheimer's disease. Neurobiol Dis. 2019 Sep 05;:104603 Authors: Caleb AA, Akiyama T, Kimura A, Kimura Y, Takahashi-Jitsuki A, Nakamura H, Makihara H, Masukawa D, Nakabayashi J, Hirano H, Nakamura F, Saito T, Saido T, Goshima Y Abstract Alzheimer's disease (AD) is an incurable neurodegenerative disease characterized by memory loss and neurotoxic amyloid beta (Aβ) plaques accumulation. Numerous pharmacological interventions targeting Aβ plaques accumulation have failed to alleviate AD. Also, the pathological alterations in AD start years before the onset of clinical symptoms. To identify proteins at play during the early stage of AD, we conducted proteomic analysis of the hippocampus of young AppNL-F mice model of AD at the preclinical phase of the disease. This was followed by interactome ranking of the proteome into hubs that were further validated in vivo using immunoblot analysis. We also performed double-immunolabeling of these hub proteins and Aβ to quantify colocalization. Behavioral analysis revealed no significant difference in memory performance between 8-month-old AppNL-F and control mice. The upregulation and downregulation of several proteins were observed in the AppNL-F mice compared to control. These proteins corresponded to pathways and processes related to Aβ clearance, inflammatory-imm...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research