Brain-derived neurotrophic factor (BDNF) and TrkB hippocampal gene expression are putative predictors of neuritic plaque and neurofibrillary tangle pathology

Neurobiology of Disease

Moses V. Chao¹  Melissa J. Alldred²  Michael H. Malek-Ahmadi³  Kewei Chen⁴  Yinghua Chen⁵  Scott E. Counts⁶  Stephen D. Ginsberg⁷  Elliott J. Mufson⁷ 

[1] Corresponding author at: Center for Dementia Research, Nathan Kline Institute, New York University Langone Medical Center, 140 Old Orangeburg Road, Orangeburg, NY 10962, United States of America.;;Department of Neuroscience &Department of Psychiatry, New York University Langone Medical Center, New York, NY, United States of America;NYU Neuroscience Institute, New York University Langone Medical Center, New York, NY, United States of America;Physiology, New York University Langone Medical Center, New York, NY, United States of America;Banner Alzheimer's Institute, Phoenix, AZ, United States of America;Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, United States of America;

关键词: Alzheimer's disease;    Brain-derived neurotrophic factor;    Microarray;    Mild cognitive impairment;    Neuritic plaques;    Neurofibrillary tangles;   

DOI  :  

来源: DOAJ

【 摘 要 】

Introduction: Downregulation of brain-derived neurotrophic factor (BDNF) and its cognate neurotrophin receptor, TrkB, were observed during the progression of dementia, but whether the Alzheimer's disease (AD) pathological lesions diffuse plaques, (DPs), neuritic plaques (NPs), and neurofibrillary tangles (NFTs) are related to this alteration remains to be clarified. Methods: Negative binomial (NB) regressions were performed using gene expression data accrued from a single population of CA1 pyramidal neurons and regional hippocampal dissections obtained from participants in the Rush Religious Orders Study (RROS). Results: Downregulation of Bdnf is independently associated with increased entorhinal cortex NPs. Downregulation of TrkB is independently associated with increased entorhinal cortex NFTs and CA1 NPs during the progression of AD. Discussion: Results indicate that BDNF and TrkB dysregulation contribute to AD neuropathology, most notably hippocampal NPs and NFTs. These data suggest attenuating BDNF/TrkB signaling deficits either at the level of BDNF, TrkB, or downstream of TrkB signaling may abrogate NPs and/or NFTs.

【 授权许可】

Unknown