“Blood-brain barrier permeable β-blockers association with Alzheimer’s disease cerebrospinal fluid biomarkers levels in non-demented individuals”
Authors: 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, and for the Alzheimer’s Disease Neuroimaging Initiative, and the European Prevention of Alzheimer’s Disease (EPAD) Consortium
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.
“Blood-brain barrier permeable β-blockers association with Alzheimer’s disease cerebrospinal fluid biomarkers levels in non-demented individuals” Authors: 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, and for the Alzheimer’s Disease Neuroimaging Initiative, and the European Prevention of Alzheimer’s Disease (EPAD)…
“Soluble Aβ pathology predicts neurodegeneration and cognitive decline independently on p-tau in the earliest Alzheimer’s continuum: Evidence across two independent cohorts”
Authors: Raffaele Cacciaglia, Carles Falcón, Gonzalo Sánchez Benavides, Anna Brugulat-Serrat, Marta Milà Alomà, Marc Suárez Calvet, José Luis Molinuevo, Karine Fauria, Carolina Minguillón, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Kaj Blennow, Henrik Zetterberg, Luigi Lorenzini, Alle Meije Wink, Silvia Ingala, Frederik Barkhof, Craig W. Ritchie, Juan Domingo Gispert, for the ALFA study
Abstract:
Introduction: Identifying the link between early Alzheimer’s disease (AD) pathological changes and neurodegeneration in asymptomatic individuals may lead to the discovery of preventive strategies. We assessed longitudinal brain atrophy and cognitive decline as a function of cerebrospinal fluid (CSF) AD biomarkers in two independent cohorts of cognitively unimpaired (CU) individuals.
Methods: We used longitudinal voxel-based morphometry (VBM) in combination with hippocampal subfield segmentation. Changes in neuroimaging and cognitive variables were inspected using general linear models (GLMs) adjusting by age, sex, apolipoprotein E (APOE) status, follow-up time, and years of education.
Results: In both cohorts, baseline CSF amyloid beta (Aβ) biomarkers significantly predicted medial temporal lobe (MTL) atrophy rates and episodic memory (EM) decline independently of CSF phosphorylated tau (p-tau).
Discussion: Our data suggest that soluble Aβ dyshomeostasis triggers MTL longitudinal atrophy and EM decline independently of CSF p-tau. Our data underscore the need for secondary preventive strategies at the earliest stages of the AD pathological cascade.
Highlights: Our results underscore the importance of undertaking Alzheimer’s preclinical trials. We assessed brain atrophy and cognitive decline in asymptomatic individuals. Aβ biomarkers predicted MTL atrophy independently of p-tau.
“Soluble Aβ pathology predicts neurodegeneration and cognitive decline independently on p-tau in the earliest Alzheimer’s continuum: Evidence across two independent cohorts” Authors: Raffaele Cacciaglia, Carles Falcón, Gonzalo Sánchez Benavides, Anna Brugulat-Serrat, Marta Milà Alomà, Marc Suárez Calvet, José Luis Molinuevo, Karine Fauria, Carolina Minguillón, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Kaj Blennow, Henrik Zetterberg, Luigi Lorenzini, Alle Meije Wink, Silvia Ingala, Frederik Barkhof, Craig W. Ritchie, Juan Domingo Gispert, for the ALFA study Abstract: Introduction: Identifying…
“Grey-Matter Structure Markers of Alzheimer’s Disease, Alzheimer’s Conversion, Functioning and Cognition: A Meta-Analysis Across 11 Cohorts”
Authors: Baptiste Couvy-Duchesne, Vincent Frouin, Vincent Bouteloup, Nikitas Koussis, Julia Sidorenko, Jiyang Jiang, Alle Meije Wink, Luigi Lorenzini, Frederik Barkhof, Julian N. Trollor, Jean-François Mangin, Perminder S. Sachdev, Henry Brodaty, Michelle K. Lupton, Michael Breakspear, Olivier Colliot, Peter M. Visscher, Naomi R. Wray, for the Alzheimer’s Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of ageing, the Alzheimer’s Disease Repository Without Borders Investigators, the MEMENTO cohort Study Group
Abstract:
Alzheimer’s disease (AD) brain markers are needed to select people with early-stage AD for clinical trials and as quantitative endpoint measures in trials. Using 10 clinical cohorts (N = 9140) and the community volunteer UK Biobank (N = 37,664) we performed region of interest (ROI) and vertex-wise analyses of grey-matter structure (thickness, surface area and volume). We identified 94 trait-ROI significant associations, and 307 distinct cluster of vertex-associations, which partly overlap the ROI associations. For AD versus controls, smaller hippocampus, amygdala and of the medial temporal lobe (fusiform and parahippocampal gyri) was confirmed and the vertex-wise results provided unprecedented localisation of some of the associated region. We replicated AD associated differences in several subcortical (putamen, accumbens) and cortical regions (inferior parietal, postcentral, middle temporal, transverse temporal, inferior temporal, paracentral, superior frontal). These grey-matter regions and their relative effect sizes can help refine our understanding of the brain regions that may drive or precede the widespread brain atrophy observed in AD. An AD grey-matter score evaluated in independent cohorts was significantly associated with cognition, MCI status, AD conversion (progression from cognitively normal or MCI to AD), genetic risk, and tau concentration in individuals with none or mild cognitive impairments (AUC in 0.54–0.70, p-value < 5e-4). In addition, some of the grey-matter regions associated with cognitive impairment, progression to AD (‘conversion’), and cognition/functional scores were also associated with AD, which sheds light on the grey-matter markers of disease stages, and their relationship with cognitive or functional impairment. Our multi-cohort approach provides robust and fine-grained maps the grey-matter structures associated with AD, symptoms, and progression, and calls for even larger initiatives to unveil the full complexity of grey-matter structure in AD.
“Grey-Matter Structure Markers of Alzheimer’s Disease, Alzheimer’s Conversion, Functioning and Cognition: A Meta-Analysis Across 11 Cohorts” Authors: Baptiste Couvy-Duchesne, Vincent Frouin, Vincent Bouteloup, Nikitas Koussis, Julia Sidorenko, Jiyang Jiang, Alle Meije Wink, Luigi Lorenzini, Frederik Barkhof, Julian N. Trollor, Jean-François Mangin, Perminder S. Sachdev, Henry Brodaty, Michelle K. Lupton, Michael Breakspear, Olivier Colliot, Peter M.…
