Decreased brain-derived neurotrophic factor depends on amyloid aggregation state in transgenic mouse models of Alzheimer's disease
Document Type
Article
Abstract
Downregulation of brain-derived neurotrophic factor (BDNF) in the cortex occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival, synaptic plasticity, and memory, BDNF reduction may contribute to synaptic and cellular loss and memory deficits characteristic of AD. In vitro evidence suggests that amyloid-β (Aβ) contributes to BDNF downregulation in AD, but the specific Aβ aggregation state responsible for this downregulation in vivo is unknown. In the present study, we examined cortical levels of BDNF mRNA in three different transgenic AD mouse models harboring mutations in APP resulting in Aβ overproduction, and in a genetic mouse model of Down syndrome. Two of the three Aβ transgenic strains (APPNLh and TgCRND8) exhibited significantly decreased cortical BDNF mRNA levels compared with wild-type mice, whereas neither the other strain (APPswe/PS-1) nor the Down syndrome mouse model (Ts65Dn) was affected. Only APPNLh and TgCRND8 mice expressed high Aβ42/Aβ40 ratios and larger SDS-stable Aβ oligomers (∼115 kDa). TgCRND8 mice exhibited downregulation of BDNF transcripts III and IV; transcript IV is also downregulated in AD. Furthermore, in all transgenic mouse strains, there was a correlation between levels of large oligomers, Aβ42/Aβ40, and severity of BDNF decrease. These data show that the amount and species of Aβ vary among transgenic mouse models of AD and are negatively correlated with BDNF levels. These findings also suggest that the effect of Aβ on decreased BDNF expression is specific to the aggregation state of Aβ and is dependent on large oligomers. Copyright © 2009 Society for Neuroscience.
Publication Date
7-22-2009
Publication Title
Journal of Neuroscience
ISSN
02706474
E-ISSN
15292401
Volume
29
Issue
29
First Page
9321
Last Page
9329
PubMed ID
19625522
Digital Object Identifier (DOI)
10.1523/JNEUROSCI.4736-08.2009
Recommended Citation
Peng, Shiyong; Garzon, Diego J.; Marchese, Monica; Klein, William; Ginsberg, Stephen D.; Francis, Beverly M.; Mount, Howard T.J.; Mufson, Elliott J.; Salehi, Ahmad; and Fahnestock, Margaret, "Decreased brain-derived neurotrophic factor depends on amyloid aggregation state in transgenic mouse models of Alzheimer's disease" (2009). Translational Neuroscience. 1771.
https://scholar.barrowneuro.org/neurobiology/1771