Increased pro–nerve growth factor and decreased brain-derived neurotrophic factor in non–Alzheimer's disease tauopathies

Alterations in the expression and signaling of brain-derived neurotrophic factor (BDNF) and the precursor to nerve growth factor (NGF), proNGF, play a role in the neuronal and cognitive dysfunction of Alzheimer's disease. Aggregated amyloid-β has been shown to down-regulate specific BDNF transcripts in Alzheimer's disease, but the role of tau pathology in neurotrophin dysregulation has not been investigated. We measured levels of BDNF mRNA and protein using real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay and proNGF protein using Western blotting in parietal cortex of subjects with tauopathies, neurodegenerative diseases exhibiting tau pathology without amyloid-β accumulation. We observed a significant increase in the level of proNGF protein in Pick's disease and a significant decrease in BDNF mRNA and protein levels in Pick's disease and corticobasal degeneration, but no neurotrophin alterations in progressive supranuclear palsy. The decrease in total BDNF mRNA levels in these tauopathies was predominantly due to down-regulation of transcript IV. These findings implicate tau pathology in neurotrophin dysregulation, which may represent a mechanism through which tau confers toxicity in Alzheimer's disease and related non-Alzheimer's dementias.