Related Experiment Video
Updated: Aug 5, 2026

Biomarker Identification for Gender Specificity of Alzheimer's Disease Based on the Glial Transcriptome Profiles
Published on: May 20, 2024
Blood Biomarkers of Alzheimer's Disease and Patterns of Structural Brain Changes in the Community
Martina Valletta1, Davide Liborio Vetrano1,2, Erika J Laukka1,2
1Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Objective:
We aimed to investigate the associations between Alzheimer's disease (AD)-related blood biomarkers and changes in brain volumes and cerebrovascular burden in community-dwelling older adults.
Methods:
We included 361 dementia-free participants with a Mini-Mental State Examination (MMSE) score ≥ 27 and without prior cerebrovascular events from a Swedish population-based study. Blood phosphorylated-tau217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured at baseline. Brain magnetic resonance imaging (MRI) was performed at baseline and after 3 and/or 6 years. Linear mixed models were used to examine associations between AD-related blood biomarkers and changes in volumes of total brain tissue (TBTV), lateral ventricles, hippocampus, amygdala, and white matter hyperintensities (WMHs).
Results:
During the follow-up, higher p-tau217 was associated with faster volume loss in the hippocampus (β*year = -0.047, 95% confidence interval [CI] = -0.077 to -0.018) and in the amygdala (β*year = -0.064, 95% CI = -0.105 to -0.022). Elevated GFAP was linked to faster TBTV decline (β*year = -0.040, 95% CI = -0.059 to -0.021), ventricular enlargement (β*year = 0.028, 95% CI = 0.013 to 0.042), and hippocampal shrinkage (β*year = -0.038, 95% CI = -0.064 to -0.013). Participants with higher NfL showed steeper TBTV decline, ventricular enlargement, hippocampal and amygdala shrinkage, and faster WMH accumulation. Results remained largely consistent after excluding participants with mild cognitive impairment at baseline.
Interpretation:
In cognitively unimpaired older adults, elevated blood p-tau217 was linked to faster shrinkage in AD-specific brain regions, whereas NfL and GFAP were associated with more widespread atrophy, with NfL also associated with accelerated WMH accumulation. These findings suggest that AD-related blood biomarkers may capture different dementia-related structural brain changes already at early stages. ANN NEUROL 2026.
Related Concept Videos
Alzheimer Disease ll: Pathophysiology
Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Alzheimer Disease l: Introduction
Dementia l: Introduction
Alzheimer's Disease: Treatment
Dementia
The progression of dementia is generally gradual.
