Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease

• Published in: Translational psychiatry Vol. 6; no. 10; p. e907
• Main Authors: Jiao, S-S, Shen, L-L, Zhu, C, Bu, X-L, Liu, Y-H, Liu, C-H, Yao, X-Q, Zhang, L-L, Zhou, H-D, Walker, D G, Tan, J, Götz, J, Zhou, X-F, Wang, Y-J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.10.2016; Nature Publishing Group
• Subjects: 631/154/436; 631/378/1595; Alzheimer Disease - drug therapy; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Animals; Behavioral Sciences; Biological Psychology; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - pharmacology; Disease Models, Animal; Gene Expression - drug effects; Gene Expression - genetics; Humans; Injections, Intraventricular; Medicine; Medicine & Public Health; Mice; Mice, Transgenic; Neurons - drug effects; Neurosciences; Original; original-article; Pharmacotherapy; Psychiatry; Synaptic Transmission - drug effects; Synaptic Transmission - genetics; Tauopathies - drug therapy; Tauopathies - genetics
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2016.186

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.