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Objective: Compare the burden of heavy metals in plasma from people with frontotemporal degeneration (FTD) and healthy controls.
Methods: A cross-sectional study of 14 FTD cases and 28 healthy controls recruited from the University of Cincinnati. Plasma samples were sent to the Trace Element Analysis Core at Dartmouth College for assessment of 24 metals or metalloids via inductively coupled plasma mass spectrometry (ICP-MS). Unconditional logistic regression models were performed with adjustments for age (centered at the median) and sex.
Results: After adjusting for age and sex, there was a significant positive association of FTD with the highest tertile of Manganese (ORadjusted = 11.1, 95% CI: 1.57-132) and Chromium (ORadjusted = 9.86, 95% CI: 1.24-218). There was significant inverse associations observed between FTD and the highest tertile of Barium (ORadjusted = 0.06, 95% CI: <0.01-0.47) and Mercury (ORadjusted = 0.13, 95% CI: 0.01-0.74), with a significant inverse trend (ptrend = 0.03).
Conclusion: Significant associations between plasma concentration of several trace metals and FTD. The significantly elevated levels of Manganese and Chromium may suggest a role of environmental exposure in the pathogenesis of FTD. However, larger, well-designed prospective studies, along with complementary experimental work, are needed to better elucidate this relationship.
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http://dx.doi.org/10.3389/fneur.2025.1593821 | DOI Listing |
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 PDFBrain
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Guangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hong Kong-Macau Institute of CNS Rege
Abnormal accumulation of TAR DNA-binding protein-43 (TDP-43) is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Small interfering RNAs (siRNAs) targeting TDP-43 offer potential therapeutic strategies for these diseases. However, efficient and safe delivery of siRNAs to the central nervous system (CNS) remains a critical challenge.
View Article and Find Full Text PDFAmyotroph Lateral Scler Frontotemporal Degener
September 2025
Faculdade de Medicina, Centro de Estudos Egas Moniz, Universidade de Lisboa, Lisboa, Portugal.
This study aimed to derive standardized regression-based (SRB) reliable change indices (RCIs) for the cognitive section of the Portuguese Edinburgh Cognitive and Behavioral ALS Screen (ECAS-C). Forty-nine MND patients undergoing the ECAS were followed-up (T1) at 7.2 ± 2 months (range = 5-12).
View Article and Find Full Text PDFCell Rep
September 2025
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA. Electronic address:
Progranulin-deficient frontotemporal dementia (GRN-FTD) is a major cause of familial FTD with TAR DNA-binding protein 43 (TDP-43) pathology, which is linked to exon dysregulation. However, little is known about this dysregulation in glial and neuronal cells. Here, using splice-junction-covering enrichment probes, we introduce single-nuclei long-read RNA sequencing 2 (SnISOr-Seq2), targeting 3,630 high-interest genes without loss of precision, and complete the first single-cell, long-read-resolved case-control study for neurodegeneration.
View Article and Find Full Text PDFAlzheimers Dement
September 2025
Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA.
Introduction: Glial fibrillary acidic protein (GFAP) may contribute to Alzheimer's pathology at early disease stages. GFAP moderation of Alzheimer's disease (AD)-related neurodegeneration and cognition is unclear.
Methods: We examined plasma GFAP moderation of AD biomarkers (amyloid beta [Aβ]-positron emission tomography [PET][A]; plasma phosphorylated tau-181 [p-tau181][T]), neurodegeneration (plasma NfL[N]; structural magnetic resonance imaging [MRI][N]), and cognition (Cog; Cog) in two cohorts: University of California San Francisco (UCSF) (N = 212, 91.