The results provide the first evidence that the miR-134-mediated post-transcriptional regulation of CREB-1 and BDNF is an important molecular mechanism underlying the plasticity deficit in AD; thus demonstrating the critical role of miR-134-5p as a potential therapeutic target for restoring plasticity in AD condition.
These results suggested that AD or MCI is accompanied by reduction of peripheral BDNF, but the levels of circulating BDNF may not be suitable as a diagnostic marker for AD and MCI.
A total of 1,081 adults without dementia (375 healthy subjects and 706 individuals with mild cognitive impairment) were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to test the influence of BDNFVal66Met polymorphism on cognitive impairment, brain structure atrophy, and change in the levels of CSF biomarkers.
The degeneration of cholinergic basal forebrain (cBF) neurons in Alzheimer's disease (AD) leads to the cognitive impairment associated with this condition. cBF neurons express the p75 neurotrophin receptor (p75<sup>NTR</sup>), which mediates cell death, and the extracellular domain of p75<sup>NTR</sup> can bind to amyloid beta (Aβ) and promote its degradation.
These data support a complex genetic interaction at loci encoding proteins implicated in the DBH-BDNF inflammatory pathway that modifies AD risk, particularly in women.
7,8-Dihydroxyflavone (7,8-DHF), as a high-affinity TrkB receptor agonist, has been extensively explored in many human disorders involving brain-derived neurotrophic factor (BDNF) such as Alzheimer's disease, Parkinson's disease, depression, and obesity.
In Alzheimer's disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF<sub>Val66Met</sub>) is associated with worse impact of primary AD pathology (beta-amyloid, Aβ) on neurodegeneration and cognitive decline, rendering BDNF<sub>Val66Met</sub> an important modulating factor of cognitive impairment in AD.
Further, gradual dysregulation of neurotrophic factors like NGF and brain derived neurotrophic factor (BDNF) have been reported during AD development thus intensifying further research in targeting these factors as disease modifying therapies against AD.
The beneficial effects of conditional BDNF production and local delivery at the location of active neuropathology highlight the potential to use endogenous biomarkers with early onset, such as astrogliosis, as regulators of neurotrophic therapy in AD.<b>SIGNIFICANCE STATEMENT</b> Recent evidence places astrocytes as pivotal players during synaptic plasticity and memory processes.
Here, we show that total sulfated GAGs from hippocampus of Alzheimer's disease have altered capacities to bind and potentiate the activities of growth factors including FGF-2, VEGF, and BDNF while their capacity to bind to tau is remarkable increased.
Additionally, there were no significant differences in serum BDNF levels between patients with AD and MCI (eight studies, <i>n</i> = 906) and between MCI and HC (nine studies, <i>n</i> = 5090).
Transplantation of BDNF modified hUC-MSCs-derived cholinergic-like neurons significantly improved spatial learning and memory abilities in the AD rats, increased the release of acetylcholine and ChAT expression in the hippocampus, enhanced the activation of astrocytes and microglia, reduced the expression of Aβ and recombinant human beta-site APP-cleaving enzyme1 (BACE1), inhibited neuronal apoptosis, and promoted neurogenesis.
BDNF total long 3' transcript expression was significantly lower in those with early AD neuropathology, compared to those without any neuropathology (p = 0.021).
Selective decline of neurotrophin and neurotrophin receptor genes within CA1 pyramidal neurons and hippocampus proper: Correlation with cognitive performance and neuropathology in mild cognitive impairment and Alzheimer's disease.
These findings indicate that physical exercise has the potential to prevent the occurrence of early emotional disturbances associated with AD and this appears to be mediated, at least in part, by modulation of hippocampal BDNF and mTOR signaling as well as through promotion of cell proliferation and survival in the hippocampal DG.
Brain-derived neurotrophic factor (BDNF) is associated with onset of several central nervous system disorders, e.g., Parkinson's disease, Alzheimer's disease, depression, epilepsy, and chronic pain.
Alzheimer's disease is marked by the presence of amyloid-beta (Aβ) plaques, elevated central cytokine levels, dysregulation of BDNF-related gene expression, and cognitive decline.
Protein-protein interaction (PPI) analysis revealed SERPINA3 and BDNF to possess high node degree interaction with literature derived candidate genes (LDGs) in AD males and females, respectively, thus were selected as potential AD targets.