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

NEUROBIOLOGY OF DISEASE

卷:132

Article

Ginsberg, Stephen D.^1,2,3,4  Malek-Ahmadi, Michael H.⁶  Alldred, Melissa J.^1,2  Chen, Yinghua⁶  Chen, Kewei⁶  Chao, Moses V.^2,4,5  Counts, Scott E.^7,8,9,10  Mufson, Elliott J.¹¹ 

[1] Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY USA

[2] NYU, Dept Psychiat, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA

[3] NYU, Dept Neurosci & Physiol, Langone Med Ctr, New York, NY USA

[4] NYU, Neurosci Inst, Langone Med Ctr, New York, NY USA

[5] NYU, Skirball Inst Biomol Med, Langone Med Ctr, New York, NY USA

[6] Banner Alzheimers Inst, Phoenix, AZ USA

[7] Michigan State Univ, Dept Translat Sci & Mol Med, Grand Rapids, MI USA

[8] Michigan State Univ, Dept Family Med, E Lansing, MI 48824 USA

[9] Michigan Alzheimers Dis Core Ctr, Ann Arbor, MI USA

[10] Mercy Hlth St Marys Hosp, Hauenstein Neurosci Ctr, Grand Rapids, MI USA

[11] Barrow Neurol Inst, Dept Neurobiol & Neurol, Phoenix, AZ 85013 USA

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

DOI  :  10.1016/j.nbd.2019.104540

来源: Elsevier

【 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.

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