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Background: Fatigue is a prevalent non-motor symptom that often appears in the early stages of Parkinson's disease (PD). Plasma neurofilament light chain (NfL) was elevated in PD patients and may be considered a potential biomarker for both motor and cognitive progression.
Objectives: In this study, we explored the association between plasma NfL levels and various fatigue subtypes and the prediction of baseline plasma NfL levels for fatigue subtype conversion.
Methods: Patients with PD were classified into four categories: persistent fatigue, never fatigue, non-persistent fatigue, and new-onset fatigue. They underwent detailed neurological evaluations at baseline and a 2-year follow-up. Plasma NfL, glial fibrillary acidic protein, phosphorylated tau181, amyloid beta 42, and Aβ40 levels in both PD patients and control subjects were measured using an ultrasensitive single molecule array.
Results: The study enrolled 174 PD patients and 95 control subjects. Plasma NfL levels were significantly higher in the persistent fatigue group compared to the never fatigue group at the 2-year follow-up ( 0.05). Longitudinally, 45.16% of baseline fatigue patients converted to non-fatigue at the 2-year follow-up. Additionally, 22.12% of patients initially without-figure patients converted to fatigue patients at the 2-year follow-up. Baseline plasma NfL levels were significantly higher in both the persistent fatigue and new-onset fatigue groups compared to the never fatigue group ( 0.05). Higher baseline NfL levels were significantly associated with new-onset fatigue (odds ratio = 1.127, = 0.034) after adjusting for confounders.
Conclusion: Baseline plasma NfL levels may serve as a biomarker for predicting fatigue subtype conversion and the progression of fatigue in PD.
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http://dx.doi.org/10.1177/17562864251324406 | 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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