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Cerebrospinal fluid neurogranin in an inducible mouse model of neurodegeneration : A translatable marker of synaptic degeneration

Höglund, Kina ; Schussler, Nathalie ; Kvartsberg, Hlin ; Smailovic, Una ; Brinkmalm, Gunnar ; Liman, Victor ; Becker, Bruno ; Zetterberg, Henrik LU ; Cedazo-Minguez, Angel and Janelidze, Shorena LU , et al. (2020) In Neurobiology of Disease 134.
Abstract

Synapse impairment is thought to be an early event in Alzheimer's disease (AD); dysfunction and loss of synapses are linked to cognitive symptoms that precede neuronal loss and neurodegeneration. Neurogranin (Ng) is a somatodendritic protein that has been shown to be reduced in brain tissue but increased in the cerebrospinal fluid (CSF) of AD patients compared to age-matched controls. High levels of CSF Ng have been shown to reflect a more rapid AD progression. To gauge the translational value of Ng as a biomarker, we developed a new, highly sensitive, digital enzyme-linked immunosorbent assay (ELISA) on the Simoa platform to measure Ng in both mouse and human CSF. We investigated and confirmed that Ng levels are increased in the CSF of... (More)

Synapse impairment is thought to be an early event in Alzheimer's disease (AD); dysfunction and loss of synapses are linked to cognitive symptoms that precede neuronal loss and neurodegeneration. Neurogranin (Ng) is a somatodendritic protein that has been shown to be reduced in brain tissue but increased in the cerebrospinal fluid (CSF) of AD patients compared to age-matched controls. High levels of CSF Ng have been shown to reflect a more rapid AD progression. To gauge the translational value of Ng as a biomarker, we developed a new, highly sensitive, digital enzyme-linked immunosorbent assay (ELISA) on the Simoa platform to measure Ng in both mouse and human CSF. We investigated and confirmed that Ng levels are increased in the CSF of patients with AD compared to controls. In addition, we explored how Ng is altered in the brain and CSF of transgenic mice that display progressive neuronal loss and synaptic degeneration following the induction of p25 overexpression. In this model, we found that Ng levels increased in CSF when neurodegeneration was induced, peaking after 2 weeks, while they decreased in brain. Our data suggest that CSF Ng is a biomarker of synaptic degeneration with translational value.

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publication status
published
subject
keywords
Alzheimer's disease, CSF biomarker, Inducible p25 mice, Neurogranin, SIMOA, Synaptic loss
in
Neurobiology of Disease
volume
134
article number
104645
publisher
Elsevier
external identifiers
  • scopus:85074236766
  • pmid:31669672
ISSN
0969-9961
DOI
10.1016/j.nbd.2019.104645
language
English
LU publication?
yes
id
8e601a60-4140-4b3d-a8b3-e4de28616c16
date added to LUP
2019-11-13 11:36:46
date last changed
2020-09-23 07:59:22
@article{8e601a60-4140-4b3d-a8b3-e4de28616c16,
  abstract     = {<p>Synapse impairment is thought to be an early event in Alzheimer's disease (AD); dysfunction and loss of synapses are linked to cognitive symptoms that precede neuronal loss and neurodegeneration. Neurogranin (Ng) is a somatodendritic protein that has been shown to be reduced in brain tissue but increased in the cerebrospinal fluid (CSF) of AD patients compared to age-matched controls. High levels of CSF Ng have been shown to reflect a more rapid AD progression. To gauge the translational value of Ng as a biomarker, we developed a new, highly sensitive, digital enzyme-linked immunosorbent assay (ELISA) on the Simoa platform to measure Ng in both mouse and human CSF. We investigated and confirmed that Ng levels are increased in the CSF of patients with AD compared to controls. In addition, we explored how Ng is altered in the brain and CSF of transgenic mice that display progressive neuronal loss and synaptic degeneration following the induction of p25 overexpression. In this model, we found that Ng levels increased in CSF when neurodegeneration was induced, peaking after 2 weeks, while they decreased in brain. Our data suggest that CSF Ng is a biomarker of synaptic degeneration with translational value.</p>},
  author       = {Höglund, Kina and Schussler, Nathalie and Kvartsberg, Hlin and Smailovic, Una and Brinkmalm, Gunnar and Liman, Victor and Becker, Bruno and Zetterberg, Henrik and Cedazo-Minguez, Angel and Janelidze, Shorena and Lefevre, Isabel A. and Eyquem, Stéphanie and Hansson, Oskar and Blennow, Kaj},
  issn         = {0969-9961},
  language     = {eng},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Cerebrospinal fluid neurogranin in an inducible mouse model of neurodegeneration : A translatable marker of synaptic degeneration},
  url          = {http://dx.doi.org/10.1016/j.nbd.2019.104645},
  doi          = {10.1016/j.nbd.2019.104645},
  volume       = {134},
  year         = {2020},
}