“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.
DOI: doi.org/10.1002/alz.14415
Published online: 3 February 2025 in the journal Alzheimer’s & Dementia: the journal of the Alzheimer’s Association