Blood-brain barrier permeable β-blockers association with Alzheimer's disease cerebrospinal fluid biomarkers levels in non-demented individuals

Mariateresa Buongiorno; Gonzalo Sánchez-Benavides; Clara Marzal-Espí; Darly Milena Giraldo; Jerzy Krupinski; Natalia Cullell; Oriol Grau-Rivera; Marc Suárez-Calvet; Juan Domingo Gispert; Alex de la Sierra; Alzheimer's Disease Neuroimaging Initiative *

doi:10.1177/13872877241293812

Blood-brain barrier permeable β-blockers association with Alzheimer's disease cerebrospinal fluid biomarkers levels in non-demented individuals

J Alzheimers Dis. 2024 Nov 25:13872877241293812. doi: 10.1177/13872877241293812. Online ahead of print.

Authors

Mariateresa Buongiorno^{1

2}, Gonzalo Sánchez-Benavides^{3

4

5}, Clara Marzal-Espí⁶, Darly Milena Giraldo^{1

2}, Jerzy Krupinski^{6

7

8}, Natalia Cullell⁷, Oriol Grau-Rivera^{3

4

5

9}, Marc Suárez-Calvet^{3

4

5

9}, Juan Domingo Gispert^{3

4

10}, Alex de la Sierra^{7

11}; Alzheimer's Disease Neuroimaging Initiative *

Affiliations

¹ Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
² Neurovascular Diseases Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
³ Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
⁴ Hospital del Mar Research Institute, Barcelona, Spain.
⁵ Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain.
⁶ Department of Neurology, Fundació Assistencial Mútua Terrassa, Terrassa, Spain.
⁷ Fundació per a Docència i Recerca, Mútua Terrassa, Terrassa, Spain.
⁸ Faculty of Science and Engineering, Department of Life Sciences John Dalton Building, Manchester Metropolitan University, Manchester, UK.
⁹ Servei de Neurologia, Hospital del Mar, Barcelona, Spain.
¹⁰ Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
¹¹ Internal Medicine Department, University Hospital Mutua de Terrassa, University of Barcelona, Terrassa, Spain.

PMID: 39584306
DOI: 10.1177/13872877241293812

Abstract

β-blockers that easily cross the blood-brain barrier (BBB) seem to diminish the risk of Alzheimer's disease (AD), hypothetically facilitating waste clearance. However, their effect on AD pathophysiological markers is unknown. We compared cerebrospinal fluid (CSF) AD biomarker levels among non-demented individuals taking low, intermediate, or high BBB permeable β-blockers in two samples (ADNI: n = 216; EPAD: n = 79). We found that CSF amyloid-β levels were higher in individuals taking highly permeable β-blockers in the ADNI sample. This result was not replicated in EPAD, in which diminished levels of pTau181 and tTau were observed. These data suggest that β-blockers may impact AD pathophysiology.

Keywords: Alzheimer's disease; amyloid-β; beta-blockers; blood-brain barrier; cerebrospinal fluid biomarkers; tau.