Stephen D Ginsberg1, Michael H Malek-Ahmadi2, Melissa J Alldred3, Yinghua Chen2, Kewei Chen2, Moses V Chao4, Scott E Counts5, Elliott J Mufson6. 1. Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, United States of America; Department of Psychiatry, New York University Langone Medical Center, New York, NY, United States of America; Department of Neuroscience & Physiology, 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. Electronic address: ginsberg@nki.rfmh.org. 2. Banner Alzheimer's Institute, Phoenix, AZ, United States of America. 3. Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, United States of America; Department of Psychiatry, New York University Langone Medical Center, New York, NY, United States of America. 4. 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; Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, NY, United States of America. 5. Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI, United States of America; Department of Family Medicine, Michigan State University, East Lansing, MI, United States of America; Michigan Alzheimer's Disease Core Center, Ann Arbor, MI, United States of America; Hauenstein Neurosciences Center, Mercy Health Saint Mary's Hospital, Grand Rapids, MI, United States of America. 6. Department of Neurobiology and Neurology, Barrow Neurological Institute, Phoenix, AZ, United States of America.
Abstract
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.
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.
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