Nilsson, J;
Cousins, KAQ;
Gobom, J;
Portelius, E;
Chen-Plotkin, A;
Shaw, LM;
Grossman, M;
... Brinkmalm, A; + view all
(2022)
Cerebrospinal fluid biomarker panel of synaptic dysfunction in Alzheimer's disease and other neurodegenerative disorders.
Alzheimer's and Dementia
10.1002/alz.12809.
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Alzheimer s Dementia - 2022 - Nilsson - Cerebrospinal fluid biomarker panel of synaptic dysfunction in Alzheimer s.pdf - Published Version Download (1MB) | Preview |
Abstract
Introduction: Synaptic degeneration is a key part of the pathophysiology of neurodegenerative diseases, and biomarkers reflecting the pathological alterations are greatly needed. Method: Seventeen synaptic proteins were quantified in a pathology-confirmed cerebrospinal fluid cohort of patients with Alzheimer's disease (AD; n = 63), frontotemporal lobar degeneration (FTLD; n = 53), and Lewy body spectrum of disorders (LBD; n = 21), as well as healthy controls (HC; n = 48). Results: Comparisons revealed four distinct patterns: markers decreased across all neurodegenerative conditions compared to HC (the neuronal pentraxins), markers increased across all neurodegenerative conditions (14-3-3 zeta/delta), markers selectively increased in AD compared to other neurodegenerative conditions (neurogranin and beta-synuclein), and markers selectively decreased in LBD and FTLD compared to HC and AD (AP2B1 and syntaxin-1B). Discussion: Several of the synaptic proteins may serve as biomarkers for synaptic dysfunction in AD, LBD, and FTLD. Additionally, differential patterns of synaptic protein alterations seem to be present across neurodegenerative diseases. Highlights: A panel of synaptic proteins were quantified in the cerebrospinal fluid using mass spectrometry. We compared Alzheimer's disease, frontotemporal degeneration, and Lewy body spectrum of disorders. Pathology was confirmed by autopsy or familial mutations. We discovered synaptic biomarkers for synaptic degeneration and cognitive decline. We found differential patterns of synaptic proteins across neurodegenerative diseases.
| Type: | Article |
|---|---|
| Title: | Cerebrospinal fluid biomarker panel of synaptic dysfunction in Alzheimer's disease and other neurodegenerative disorders |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.12809 |
| Publisher version: | https://doi.org/10.1002/alz.12809 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. See: http://creativecommons.org/licenses/by-nc/4.0/ |
| Keywords: | Alzheimer's disease, Lewy body spectrum of disorders, biomarkers, frontotemporal lobar degeneration, mass spectrometry, synaptic pathology |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10158005 |
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