title: Reducing Endogenous α-Synuclein Mitigates the Degeneration of Selective Neuronal Populations in an Alzheimer's Disease Transgenic Mouse Model.
abstract: Alzheimer's disease (AD) is characterized by the progressive accumulation of amyloid β (Aβ) and microtubule associate protein tau, leading to the selective degeneration of neurons in the neocortex, limbic system, and nucleus basalis, among others. Recent studies have shown that α-synuclein (α-syn) also accumulates in the brains of patients with AD and interacts with Aβ and tau, forming toxic hetero-oligomers. Although the involvement of α-syn has been investigated extensively in Lewy body disease, less is known about the role of this synaptic protein in AD. Here, we found that reducing endogenous α-syn in an APP transgenic mouse model of AD prevented the degeneration of cholinergic neurons, ameliorated corresponding deficits, and recovered the levels of Rab3a and Rab5 proteins involved in intracellular transport and sorting of nerve growth factor and brain-derived neurotrophic factor. Together, these results suggest that α-syn might participate in mechanisms of vulnerability of selected neuronal populations in AD and that reducing α-syn might be a potential approach to protecting these populations from the toxic effects of Aβ.
  
  
  
  Reducing endogenous α-synuclein (α-syn) in an APP transgenic mouse model of Alzheimer's disease (AD) prevented the degeneration of cholinergic neurons, ameliorated corresponding deficits, and recovered the levels of Rab3a and Rab5 proteins involved in intracellular transport and sorting of nerve growth factor and brain-derived neurotrophic factor. These results suggest that α-syn might participate in mechanisms of vulnerability of selected neuronal populations in AD and that reducing α-syn might be a potential approach to protecting these populations from the toxic effects of amyloid β.
authors.affiliation: Department of Neurosciences and.
authors.forename: Brian
authors.identifier: 0000-0002-7486-1941
authors.initials: B
authors.lastname: Spencer
authors.affiliation: Department of Neurosciences and Department of Pathology, University of California-San Diego, La Jolla, California 92093.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Desplats
authors.affiliation: Department of Neurosciences and.
authors.forename: Cassia R
authors.initials: CR
authors.lastname: Overk
authors.affiliation: Department of Neurosciences and.
authors.forename: Elvira
authors.initials: E
authors.lastname: Valera-Martin
authors.affiliation: Department of Neurosciences and.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rissman
authors.affiliation: Department of Neurosciences and.
authors.forename: Chengbiao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Neurosciences and.
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.affiliation: Department of Neurosciences and.
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.affiliation: Department of Neurosciences and.
authors.forename: Jazmin
authors.initials: J
authors.lastname: Florio
authors.affiliation: Department of Neurosciences and.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Neurosciences and Department of Pathology, University of California-San Diego, La Jolla, California 92093 emasliah@ucsd.edu.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*; D020826:rab3A GTP-Binding Protein / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D020826:rab3A GTP-Binding Protein; D020696:rab5 GTP-Binding Proteins
keywords: Alzheimer's disease; amyloid β oligomer; cholinergic neuron; selective vulnerability; transgenic animal model; α-synuclein