Neuroligin-1 in brain and CSF of neurodegenerative disorders : investigation for synaptic biomarkers
Camporesi, Elena ; Lashley, Tammaryn ; Gobom, Johan ; Lantero-Rodriguez, Juan ; Hansson, Oskar LU
; Zetterberg, Henrik
LU
; Blennow, Kaj
LU
and Becker, Bruno
(2021)
In Acta Neuropathologica Communications
9(1).
- Abstract
Synaptic pathology is a central event in Alzheimer’s disease (AD) and other neurodegenerative conditions, and investigation of synaptic proteins can provide valuable tools to follow synaptic dysfunction and loss in these diseases. Neuroligin-1 (Nlgn1) is a postsynaptic cell adhesion protein, important for synapse stabilization and formation. Nlgn1 has been connected to cognitive disorders, and specifically to AD, as target of the synaptotoxic effect of amyloid-β (Aβ) oligomers and Aβ fibrils. To address changes in Nlgn1 expression in human brain, brain regions in different neurological disorders were examined by Western blot and mass spectrometry. Brain specimens from AD (n = 23), progressive supranuclear palsy (PSP, n = 11),... (More)
Synaptic pathology is a central event in Alzheimer’s disease (AD) and other neurodegenerative conditions, and investigation of synaptic proteins can provide valuable tools to follow synaptic dysfunction and loss in these diseases. Neuroligin-1 (Nlgn1) is a postsynaptic cell adhesion protein, important for synapse stabilization and formation. Nlgn1 has been connected to cognitive disorders, and specifically to AD, as target of the synaptotoxic effect of amyloid-β (Aβ) oligomers and Aβ fibrils. To address changes in Nlgn1 expression in human brain, brain regions in different neurological disorders were examined by Western blot and mass spectrometry. Brain specimens from AD (n = 23), progressive supranuclear palsy (PSP, n = 11), corticobasal degeneration (CBD, n = 10), and Pick’s disease (PiD, n = 9) were included. Additionally, cerebrospinal fluid (CSF) samples of AD patients (n = 43) and non-demented controls (n = 42) were analysed. We found decreased levels of Nlgn1 in temporal and parietal cortex (~ 50–60% reductions) in AD brains compared with controls. In frontal grey matter the reduction was not seen for AD patients; however, in the same region, marked reduction was found for PiD (~ 77%), CBD (~ 66%) and to a lesser extent for PSP (~ 43%), which could clearly separate these tauopathies from controls. The Nlgn1 level was reduced in CSF from AD patients compared to controls, but with considerable overlap. The dramatic reduction of Nlgn1 seen in the brain extracts of tauopathies warrants further investigation regarding the potential use of Nlgn1 as a biomarker for these neurodegenerative diseases.
(Less)
- author
- Camporesi, Elena
; Lashley, Tammaryn
; Gobom, Johan
; Lantero-Rodriguez, Juan
; Hansson, Oskar
LU
; Zetterberg, Henrik
LU
; Blennow, Kaj
LU
and Becker, Bruno
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer’s disease, Neuroligin-1, Synapse loss, Tauopathies
- in
- Acta Neuropathologica Communications
- volume
- 9
- issue
- 1
- article number
- 19
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:33522967
- scopus:85100311109
- ISSN
- 2051-5960
- DOI
- 10.1186/s40478-021-01119-4
- language
- English
- LU publication?
- yes
- id
- ed2dffcf-ee39-45e2-85bb-c0db936a85d7
- date added to LUP
- 2021-02-11 08:55:11
- date last changed
- 2024-06-27 08:32:48
@article{ed2dffcf-ee39-45e2-85bb-c0db936a85d7,
abstract = {{<p>Synaptic pathology is a central event in Alzheimer’s disease (AD) and other neurodegenerative conditions, and investigation of synaptic proteins can provide valuable tools to follow synaptic dysfunction and loss in these diseases. Neuroligin-1 (Nlgn1) is a postsynaptic cell adhesion protein, important for synapse stabilization and formation. Nlgn1 has been connected to cognitive disorders, and specifically to AD, as target of the synaptotoxic effect of amyloid-β (Aβ) oligomers and Aβ fibrils. To address changes in Nlgn1 expression in human brain, brain regions in different neurological disorders were examined by Western blot and mass spectrometry. Brain specimens from AD (n = 23), progressive supranuclear palsy (PSP, n = 11), corticobasal degeneration (CBD, n = 10), and Pick’s disease (PiD, n = 9) were included. Additionally, cerebrospinal fluid (CSF) samples of AD patients (n = 43) and non-demented controls (n = 42) were analysed. We found decreased levels of Nlgn1 in temporal and parietal cortex (~ 50–60% reductions) in AD brains compared with controls. In frontal grey matter the reduction was not seen for AD patients; however, in the same region, marked reduction was found for PiD (~ 77%), CBD (~ 66%) and to a lesser extent for PSP (~ 43%), which could clearly separate these tauopathies from controls. The Nlgn1 level was reduced in CSF from AD patients compared to controls, but with considerable overlap. The dramatic reduction of Nlgn1 seen in the brain extracts of tauopathies warrants further investigation regarding the potential use of Nlgn1 as a biomarker for these neurodegenerative diseases.</p>}},
author = {{Camporesi, Elena and Lashley, Tammaryn and Gobom, Johan and Lantero-Rodriguez, Juan and Hansson, Oskar and Zetterberg, Henrik and Blennow, Kaj and Becker, Bruno}},
issn = {{2051-5960}},
keywords = {{Alzheimer’s disease; Neuroligin-1; Synapse loss; Tauopathies}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Acta Neuropathologica Communications}},
title = {{Neuroligin-1 in brain and CSF of neurodegenerative disorders : investigation for synaptic biomarkers}},
url = {{http://dx.doi.org/10.1186/s40478-021-01119-4}},
doi = {{10.1186/s40478-021-01119-4}},
volume = {{9}},
year = {{2021}},
}