title: N-terminal region of myelin basic protein reduces fibrillar amyloid-β deposition in Tg-5xFAD mice.
abstract: Alzheimer's disease is a progressive neurodegenerative disorder that is characterized by extensive deposition of fibrillar amyloid-β (Aβ) in the brain. Previously, myelin basic protein (MBP) was identified to be a potent inhibitor to Aβ fibril formation, and this inhibitory activity was localized to the N-terminal residues 1-64, a fragment designated MBP1. Here, we show that the modest neuronal expression of a fusion protein of the biologically active MBP1 fragment and the enhanced green fluorescent protein (MBP1-EGFP) significantly improved the performance of spatial learning memory in Tg-5xFAD mice, a model of pathologic Aβ accumulation in brain. The levels of insoluble Aβ and fibrillar amyloid were significantly reduced in bigenic Tg-5xFAD/Tg-MBP1-EGFP mice. Quantitative stereological analysis revealed that the reduction in amyloid was because of a reduction in the size of fibrillar plaques rather than a decrease in plaque numbers. The current findings support previous studies showing that MBP1 inhibits Aβ fibril formation in vitro and demonstrate the ability of MBP1 to reduce Aβ pathology and improve behavioral performance.
authors.affiliation: Department of Neurosurgery, Health Sciences Center, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Ming-Hsuan
authors.initials: MH
authors.lastname: Ou-Yang
authors.affiliation: Department of Neurosurgery, Health Sciences Center, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Health Sciences Center, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Mei-Chen
authors.initials: MC
authors.lastname: Liao
authors.affiliation: Department of Neurosurgery, Health Sciences Center, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Judianne
authors.initials: J
authors.lastname: Davis
authors.affiliation: Department of Psychology, Health Sciences Center, Stony Brook University, Stony Brook, NY, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Robinson
authors.affiliation: Department of Neurosurgery, Health Sciences Center, Stony Brook University, Stony Brook, NY, USA; Department of Medicine, Health Sciences Center, Stony Brook University, Stony Brook, NY, USA. Electronic address: William.VanNostrand@sbumed.org.
authors.forename: William E
authors.initials: WE
authors.lastname: Van Nostrand
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001519:Behavior; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000737:chemistry / Q000502:physiology*; D066263:Protein Aggregation, Pathological / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D004676:Myelin Basic Protein
keywords: Alzheimer's disease; Amyloid β-protein; Myelin basic protein; Transgenic mice