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Recent investigations implicate neuroinflammatory changes, including astrocyte and microglia activation, as crucial in the progression of Alzheimer's disease (AD) Thus, we compared selected proteins reflecting neuroinflammatory processes to establish their connection to AD pathologies. Our study, encompassing 80 subjects with ( = 42) AD, ( = 18) mild cognitive impairment (MCI) and ( = 20) non-demented controls compares the clinical potential of tested molecules. Using antibody-based methods, we assessed concentrations of NGAL, CXCL-11, sTREM1, and sTREM2 in cerebrospinal fluid (CSF). Proinflammatory proteins, NGAL, and CXCL-11 reached a peak in the early stage of the disease and allowed for the identification of patients with MCI. Furthermore, the concentration of the anti-inflammatory molecule sTREM2 was highest in the more advanced stage of the disease and permitted differentiation between AD and non-demented controls. Additionally, sTREM2 was biochemically linked to tau and pTau in the AD group. Notably, NGAL demonstrated superior diagnostic performance compared to classical AD biomarkers in discriminating MCI patients from controls. These findings suggest that proteins secreted mainly through microglia dysfunction might play not only a detrimental but also a protective role in the development of AD pathology.
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http://dx.doi.org/10.3390/ijms25147543 | DOI Listing |
Parkinsonism 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.
JMIR Mhealth Uhealth
September 2025
Department of Neurology, School of Medicine, Washington University in St. Louis, 660 South Euclid Avenue, St Louis, MO, 63130, United States, 1 9548065162.
Background: Unsupervised cognitive assessments are becoming commonly used in studies of aging and neurodegenerative diseases. As assessments are completed in everyday environments and without a proctor, there are concerns about how common distractions may impact performance and whether these distractions may differentially impact those experiencing the earliest symptoms of dementia.
Objective: We examined the impact of self-reported interruptions, testing location, and social context during testing on remote cognitive assessments in older adults.
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 PDFAm J Respir Cell Mol Biol
September 2025
University of Toronto, Interdepartmental Division of Critical Care Medicine, Toronto, Ontario, Canada.
Post-Intensive Care Syndrome (PICS) is a serious condition involving physical weakness, depression, and cognitive impairment that develop during or after an intensive care unit (ICU) stay, often resulting in long-term declines in quality of life. Patients with acute respiratory distress syndrome (ARDS) and severe COVID-19 are at particularly high risk, yet the molecular mechanisms underlying PICS remain poorly understood. Here, we identify impaired Apelin-APJ signaling as a potential contributor to PICS pathogenesis via disruption of inter-organ homeostasis.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Neuroscience, The Scripps Research Institute, San Diego, CA 92037.
Microglia regulate neuronal circuit plasticity. Disrupting their homeostatic function has detrimental effects on neuronal circuit health. Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, including Alzheimer's disease (AD), with several microglial activation genes linked to increased risk for these conditions.
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