Soluble Aβ Pathology Predicts Neurodegeneration and Cognitive Decline Independently on P-tau in the Earliest Alzheimer's Continuum: Evidence Across Two Independent Cohorts

Overview

Journal Alzheimers Dement

Date 2025 Feb 3

PMID 39898436

Authors

Raffaele Cacciaglia

Carles Falcon

Gonzalo Sanchez Benavides

Anna Brugulat-Serrat

Marta Mila Aloma

Marc Suarez Calvet

Jose Luis Molinuevo

Karine Fauria

Carolina Minguillon

Gwendlyn Kollmorgen

Clara Quijano-Rubio

Kaj Blennow

Henrik Zetterberg

Luigi Lorenzini

Alle Meije Wink

Silvia Ingala

Frederik Barkhof

Craig W Ritchie

Juan Domingo Gispert

Affiliations

Soon will be listed here.

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: We assessed brain atrophy and cognitive decline in asymptomatic individuals. Aβ biomarkers predicted MTL atrophy independently of p-tau. Our results underscore the importance of undertaking Alzheimer's preclinical trials.

Citing Articles

Soluble Aβ pathology predicts neurodegeneration and cognitive decline independently on p-tau in the earliest Alzheimer's continuum: Evidence across two independent cohorts.

Cacciaglia R, Falcon C, Benavides G, Brugulat-Serrat A, Aloma M, Calvet M Alzheimers Dement. 2025; 21(2):e14415.

PMID: 39898436 PMC: 11848178. DOI: 10.1002/alz.14415.

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