Bellaver, B;
Puig-Pijoan, A;
Ferrari-Souza, JP;
Leffa, DT;
Lussier, FZ;
Ferreira, PCL;
Tissot, C;
... Pascoal, TA; + view all
(2023)
Blood-brain barrier integrity impacts the use of plasma amyloid-β as a proxy of brain amyloid-β pathology.
Alzheimer's and Dementia
, 19
(9)
pp. 3815-3825.
10.1002/alz.13014.
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Abstract
INTRODUCTION: Amyloid-β (Aβ) and tau can be quantified in blood. However, biological factors can influence the levels of brain-derived proteins in the blood. The blood-brain barrier (BBB) regulates protein transport between cerebrospinal fluid (CSF) and blood. BBB altered permeability might affect the relationship between brain and blood biomarkers. METHODS: We assessed 224 participants in research (TRIAD, n = 96) and clinical (BIODEGMAR, n = 128) cohorts with plasma and CSF/positron emission tomography Aβ, p-tau, and albumin measures. RESULTS: Plasma Aβ42/40 better identified CSF Aβ42/40 and Aβ-PET positivity in individuals with high BBB permeability. An interaction between plasma Aβ42/40 and BBB permeability on CSF Aβ42/40 was observed. Voxel-wise models estimated that the association of positron emission tomography (PET), with plasma Aβ was most affected by BBB permeability in AD-related brain regions. BBB permeability did not significantly impact the relationship between brain and plasma p-tau levels. DISCUSSION: These findings suggest that BBB integrity may influence the performance of plasma Aβ, but not p-tau, biomarkers in research and clinical settings. Highlights: BBB permeability affects the association between brain and plasma Aβ levels. BBB integrity does not affect the association between brain and plasma p-tau levels. Plasma Aβ was most affected by BBB permeability in AD-related brain regions. BBB permeability increases with age but not according to cognitive status.
| Type: | Article |
|---|---|
| Title: | Blood-brain barrier integrity impacts the use of plasma amyloid-β as a proxy of brain amyloid-β pathology |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.13014 |
| Publisher version: | https://doi.org/10.1002/alz.13014 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer's disease, amyloid-β, blood biomarkers, blood-brain barrier, confounding factors |
| 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.ucl.ac.uk/id/eprint/10168688 |
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