title: Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease.
abstract: Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques consisting of amyloid-beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aβ-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established. Here, we found that the BDNF level was reduced in the serum and brain of AD patients and P301L transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved stable expression of BDNF gene and restored the BDNF level in the brains of P301L mice. Restoration of the BDNF level attenuated behavioral deficits, prevented neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality, but did not affect tau hyperphosphorylation level in the brains of P301L mice. Long-term expression of AAV-BDNF in the brain was well tolerated by the mice. These findings suggest that the gene delivery of BDNF is a promising treatment for tau-related neurodegeneration for AD and other neurodegenerative disorders with tauopathy.
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.|Cadre Ward, Department of Neurology, Bethune International Peace Hospital, Shijiazhuang, China.
authors.forename: S-S
authors.initials: SS
authors.lastname: Jiao
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: L-L
authors.initials: LL
authors.lastname: Shen
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: X-L
authors.initials: XL
authors.lastname: Bu
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: C-H
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Yao
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: L-L
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: H-D
authors.initials: HD
authors.lastname: Zhou
authors.affiliation: Laboratory of Neuroinflammation, Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Walker
authors.affiliation: Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tan
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Götz
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute, Division of Health Sciences, University of South Australia, Adelaide, SA, Australia.
authors.forename: X-F
authors.initials: XF
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007276:Injections, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D024801:Tauopathies / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human