PMID- 31882186
OWN - NLM
STAT- MEDLINE
DCOM- 20200914
LR  - 20210226
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 87
DP  - 2020 Mar
TI  - Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer's disease.
PG  - 49-59
LID - S0197-4580(19)30409-9 [pii]
LID - 10.1016/j.neurobiolaging.2019.11.010 [doi]
AB  - Disruption of brain-derived neurotrophic factor (BDNF) biosynthesis and/or 
      signaling has been implicated in the pathogenesis of Alzheimer's disease (AD). We 
      used postmortem brain and fluid samples from 20 patients with variable severity 
      of AD and 11 controls to investigate whether BDNF levels in serum and brain 
      tissue correlated with hippocampal pathology. Total BDNF, precursor BDNF 
      (pro-BDNF), and mature BDNF were measured in cerebrospinal fluid, serum, and 3 
      postmortem brain regions. Histological markers for AD pathology, the BDNF cognate 
      receptor (TrkB), and glia were measured in the hippocampus (HIP). Lower pro-BDNF 
      levels were observed in the entorhinal and frontal cortices in AD cases compared 
      with controls. AD cases also exhibited significantly lower staining densities of 
      the cognate BDNF receptor TrkB in the HIP compared with controls, and TrkB 
      staining was inversely correlated with both Amylo-Glo and pTau staining in the 
      same region, suggesting a relationship between the density of the cognate BDNF 
      receptor and accumulation of AD pathology. In addition, higher serum pro-BDNF 
      levels correlated with lower HIP pro-BDNF levels and higher pTau staining in the 
      HIP. Total BDNF levels in cortical regions were also negatively correlated with 
      Amylo-Glo staining in the HIP suggesting that reduced BDNF cortical levels might 
      influence hippocampal amyloid accumulation. These results strongly suggest that 
      altered BDNF and TrkB receptors are involved in AD pathology and therefore 
      warrant investigations into therapies involving the BDNF pathway.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Bharani, Krishna L
AU  - Bharani KL
AD  - Department of Neurosciences, Medical University of South Carolina, Charleston, 
      SC, USA.
FAU - Ledreux, Aurelie
AU  - Ledreux A
AD  - Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA.
FAU - Gilmore, Anah
AU  - Gilmore A
AD  - Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA.
FAU - Carroll, Steven L
AU  - Carroll SL
AD  - Department of Pathology and Laboratory Medicine, Medical University of South 
      Carolina, Charleston, SC, USA.
FAU - Granholm, Ann-Charlotte
AU  - Granholm AC
AD  - Department of Neurosciences, Medical University of South Carolina, Charleston, 
      SC, USA; Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, 
      USA. Electronic address: Lotta.Granholm-Bentley@du.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191122
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Protein Precursors)
RN  - 0 (brain-derived neurotrophic factor precursor)
RN  - 0 (tau Proteins)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*etiology/*metabolism/pathology
MH  - Amyloid beta-Peptides/metabolism
MH  - Brain-Derived Neurotrophic Factor/blood/*metabolism
MH  - Female
MH  - Hippocampus/*metabolism/pathology
MH  - Humans
MH  - Male
MH  - Membrane Glycoproteins/metabolism
MH  - Middle Aged
MH  - Phosphorylation
MH  - Protein Precursors/blood/*metabolism
MH  - Receptor, trkB/metabolism
MH  - Staining and Labeling/*methods
MH  - tau Proteins/*metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - BDNF
OT  - Hippocampus
OT  - Neurotrophic factors
OT  - Pro-BDNF
OT  - TrkB
EDAT- 2019/12/29 06:00
MHDA- 2020/09/15 06:00
CRDT- 2019/12/29 06:00
PHST- 2019/05/15 00:00 [received]
PHST- 2019/11/02 00:00 [revised]
PHST- 2019/11/15 00:00 [accepted]
PHST- 2019/12/29 06:00 [pubmed]
PHST- 2020/09/15 06:00 [medline]
PHST- 2019/12/29 06:00 [entrez]
AID - S0197-4580(19)30409-9 [pii]
AID - 10.1016/j.neurobiolaging.2019.11.010 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2020 Mar;87:49-59. doi: 10.1016/j.neurobiolaging.2019.11.010. 
      Epub 2019 Nov 22.