Genetic Knockdown of Brain-Derived Neurotrophic Factor in 3xTg-AD Mice Does Not Alter Aβ or Tau Pathology
Year: 2012
Type: article
Abstract: Brain-derived neurotrophic factor (BDNF) is a neurotrophin critically involved in cell survival, synaptic plasticity, and memory. BDNF has recently garnered significant attention as a potential therapeutic target for neurodegenerative diseases such as Alzheimer disease (AD), but emerging evidence suggests that BDNF may also be mechanistically involved in the pathogenesis of AD. AD patients have substantially reduced BDNF levels, which may be a result of Aβ and tau pathology. Recent evidence, however, indicates reduced BDNF levels may also serve to drive pathology in neuronal cultures, although this has not yet been established in vivo. To further investigate the mechanistic role of BDNF in AD, we generated 3xTg-AD mice with a heterozygous BDNF knockout (BDNF(+/-)) and analyzed Aβ and tau pathology. Aged 3xTg-AD/BDNF(+/-) mice have significantly reduced levels of brain BDNF, but have comparable levels of Aβ and tau pathology to 3xTg-AD/BDNF(+/+) mice. These findings indicate that chronic reduction of BDNF does not exacerbate the development of Aβ and tau pathology, and instead suggests the reduced BDNF levels found in AD patients are a consequence of these pathologies.
Source: PLoS ONE
Institution: University of California, Irvine
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
OpenAlex ID: W2170013728