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Introduction: Both micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.
Methods: Thirty cognitively stable (CS) adults with DS underwent diffusion-weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts were derived using automatic fiber tracking, and associations with plasma NfL were assessed using Spearman correlation coefficients.
Results: Higher Plasma NfL was associated with greater altered diffusion measures of select tracts.
Discussion: Early increases in plasma NfL may reflect early white matter microstructural changes prior to dementia in DS.
Highlights: The onset of such WM changes in DS has not yet been widely studied.WM microstructural properties correlated with plasma neurofilament light chain (NfL).NfL may reflect early, selective WM changes in adults with DS at high risk of developing AD.
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http://dx.doi.org/10.1002/dad2.70023 | DOI Listing |
Mol Psychiatry
September 2025
Memory Center, Hospital Moinhos de Vento, Porto Alegre, RS, Brazil.
Blood-based biomarkers (BBMs) have emerged as promising tools to enhance Alzheimer's disease (AD) diagnosis. Despite two-thirds of dementia cases occurring in the Global South, research on BBMs has predominantly focused on populations from the Global North. This geographical disparity hinders our understanding of BBM performance in diverse populations.
View Article and Find Full Text PDFParkinsonism Relat Disord
September 2025
Translational and Clinical Research Institute, Newcastle University, UK.
Introduction: Dysfunction of the glymphatic system is thought to lead to build up of toxic proteins including β-amyloid and α-synuclein, and thus may be involved in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). The Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS) index has been proposed as a marker of glymphatic function.
Aims: To investigate DTI-ALPS in mild cognitive impairment (MCI) and dementia, and determine its relationship with cognitive decline, and biomarkers of neurodegeneration.
Neurology
October 2025
Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic de Barcelona, Fundació Recerca Clínic Barcelona-IDIBAPS, Spain.
Background And Objectives: α-Synuclein seed amplification assays (αSAAs) can improve the diagnosis of synucleinopathies and detect α-synuclein (αSyn) copathology in vivo in clinical practice. We aimed to evaluate the diagnostic performance of αSAA for detecting αSyn in CSF for diagnosing dementia with Lewy bodies (DLB) in a clinical cohort of cognitively impaired individuals. We explored how the coexistence of Alzheimer disease (AD) and αSyn pathology influences biomarker levels and clinical profiles.
View Article and Find Full Text PDFJ Neurochem
September 2025
Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Elucidating the earliest biological mechanisms underlying Alzheimer's disease (AD) is critical for advancing early detection strategies. While amyloid-β (Aβ) and tau pathologies have been central to preclinical AD research, the roles of peripheral biological processes in disease initiation remain underexplored. We investigated patterns of F-MK6240 tau positron emission tomography (PET) and peripheral inflammation across stages defined by Aβ burden and neuronal injury in n = 132 (64.
View Article and Find Full Text PDFGeroscience
September 2025
Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Kangwon, 24341, Republic of Korea.
Alzheimer's disease (AD) represents a growing global health burden, underscoring the urgent need for reliable diagnostic and prognostic biomarkers. Although several disease-modifying treatments have recently become available, their effects remain limited, as they primarily delay rather than halt disease progression. Thus, the early and accurate identification of individuals at elevated risk for conversion to AD dementia is crucial to maximize the effectiveness of these therapies and to facilitate timely intervention strategies.
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