Background: Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset. Identifying candidate predictors to forecast AD dementia risk before disease onset is crucial for early diagnosis and treatment.
Objective: We aimed to assess the predictive ability of blood neurofilament light (NfL) chain in anticipating cognitive decline in the AD continuum.
Methods: We systematically searched PubMed, Web of Science, and Embase from inception until April 7, 2023. Longitudinal observational studies examining the association between baseline blood NfL and cognitive decline or clinical disease conversion were included based on inclusion/exclusion criteria. The final effect size was represented by adjusted hazard ratios (HR) or standardized beta (s.β) coefficients with a 95% confidence interval (CI).
Results: A total of 2,862 articles were identified, and 26 studies were included in this meta-analysis. The results indicated that baseline blood NfL could predict cognitive decline, with MMSE [s.β= -0.17, 95% CI (-0.26, -0.07)]; PACC [s.β= -0.09, 95% CI (-0.16, -0.03)]; ADAS-cog [s.β= 0.21, 95% CI (0.13, 0.29)]; CDR-SOB [s.β= 0.27, 95% CI (0.03, 0.50)]; Global cognitive composite [s.β= -0.05, 95% CI (-0.08, -0.01)]; Memory subdomain [s.β= -0.06, 95% CI (-0.09, -0.03)]; Language subdomain [s.β= -0.07, 95% CI (-0.10, -0.05)]; Executive function subdomain [s.β= -0.02, 95% CI (-0.03, -0.01)]; Visuospatial subdomain [s.β= -0.06, 95% CI (-0.08, -0.04)]. Additionally, baseline blood NfL could predict disease progression (conversion from CU/SCD/MCI to MCI/AD) in the AD continuum [Adjust HR = 1.32, 95% CI (1.12, 1.56)].
Conclusions: Baseline blood NfL demonstrated predictive capabilities for global cognition and its memory, language, executive function, visuospatial subdomains decline in the AD continuum. Moreover, it exhibited the potential to predict disease progression in non-AD dementia participants.
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http://dx.doi.org/10.3233/JAD-231080 | DOI Listing |
Sci Transl Med
January 2025
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, 81377 Munich, Germany.
In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, United States of America.
Many psychiatric disorders and associated psychopathology dimensions are related to social cognitive deficits and reduced general cognitive ability. The current study applied a hierarchical, dimensional approach to better understand associations among psychopathology, social cognition, and general cognitive ability. Data were collected from two samples (n = 653), including psychosis-spectrum patients, their first-degree relatives, and individuals from community sources.
View Article and Find Full Text PDFJAMA Psychiatry
January 2025
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.
View Article and Find Full Text PDFCell Mol Neurobiol
January 2025
Laboratory of Neurobiology, Centro de Investigaciones Medico Sanitarias (CIMES), University of Malaga, Calle Marqués de Beccaria, 3, Campus Teatinos s/n, 29010, Malaga, Spain.
Tetrameric AMPA-type ionotropic glutamate receptors are primary transducers of fast excitatory synaptic transmission in the central nervous system, and their properties and abundance at the synaptic surface are crucial determinants of synaptic efficacy in neuronal communication across the brain. The induction of long-term potentiation (LTP) leads to the insertion of GluA1-containing AMPA receptors at the synaptic surface, whereas during long-term depression (LTD), these receptors are internalized into the cytoplasm of the spine. Disruptions in the trafficking of AMPA receptors to and from the synaptic surface attenuate both forms of synaptic plasticity.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050, P. R. China.
MicroRNAs (miRNAs) are associated with amyloid-β (Aβ) dysmetabolism, a pivotal factor in the pathogenesis of Alzheimer's disease (AD). This study unveiled a novel miRNA, microRNA-32533 (miR-32533), featuring a distinctive base sequence identified through RNA sequencing of the APPswe/PSEN1dE9 (APP/PS1) mouse brain. Its role and underlying mechanisms were subsequently explored.
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