Milà-Alomà, M;
Brinkmalm, A;
Ashton, NJ;
Kvartsberg, H;
Shekari, M;
Operto, G;
Salvadó, G;
... ALFA Study; + view all
(2021)
CSF Synaptic Biomarkers in the Preclinical Stage of Alzheimer Disease and Their Association With MRI and PET: A Cross-sectional Study.
Neurology
10.1212/WNL.0000000000012853.
(In press).
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Abstract
OBJECTIVE: To determine whether CSF synaptic biomarkers are altered in the early preclinical stage of the Alzheimer's continuum and associated with Alzheimer's disease (AD) risk factors, primary pathology, and neurodegeneration markers. METHODS: Cross-sectional study in the ALFA+ cohort, comprising middle-aged cognitively unimpaired participants. CSF neurogranin and GAP-43 were measured using immunoassays and SNAP-25 and synaptotagmin-1 using immunoprecipitation mass spectrometry. AD CSF biomarkers Aβ42/40, p-tau and t-tau, and the neurodegeneration biomarker NfL were also measured. Participants underwent structural MRI, and fluorodeoxyglucose and Aβ PET imaging. General linear modeling was used to test the associations between CSF synaptic biomarkers and risk factors, Aβ pathology, tau pathology, and neurodegeneration markers. RESULTS: All CSF synaptic biomarkers increased with age. CSF neurogranin was higher in females, while CSF SNAP-25 was higher in APOE-ε4 carriers. All CSF synaptic biomarkers increased with higher Aβ load (as measured by CSF Aβ42/40 and Aβ PET Centiloid values) and, importantly, the synaptic biomarkers were increased even in individuals in the earliest stages of Aβ deposition. Higher CSF synaptic biomarkers were also associated with higher CSF p-tau and NfL. Higher CSF neurogranin and GAP-43 were significantly associated with higher brain metabolism, but lower cortical thickness in AD-related brain regions. CONCLUSION: CSF synaptic biomarkers increase in early preclinical stages of the Alzheimer's continuum even when a low burden of Aβ pathology is present, and they differ in their association with age, sex, APOE-ε4, and markers of neurodegeneration.
| Type: | Article |
|---|---|
| Title: | CSF Synaptic Biomarkers in the Preclinical Stage of Alzheimer Disease and Their Association With MRI and PET: A Cross-sectional Study |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/WNL.0000000000012853 |
| Publisher version: | https://doi.org/10.1212/WNL.0000000000012853 |
| Language: | English |
| Additional information: | © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences 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 UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10135697 |
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