Introduction: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers.
Methods: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.
Results: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.
Discussion: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.
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http://dx.doi.org/10.1016/j.jalz.2019.03.004 | DOI Listing |
Nanomedicine (Lond)
December 2024
LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal.
Expert Opin Drug Saf
December 2024
Zhejiang Academy of Traditional Chinese Medicine, Tongde hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
Background: Aducanumab, a monoclonal antibody, received approval for the treatment of Alzheimer's disease in 2021. However, it remains controversial over the security of this drug. In this study, aducanumab-related adverse events (AEs) were evaluated through data mining based on the FDA Adverse Event Reporting System (FAERS) database.
View Article and Find Full Text PDFPNAS Nexus
January 2025
School of Chemistry & Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive NW, Atlanta, GA 30332, USA.
Recombinant antibodies are a promising class of therapeutics to treat protein misfolding associated with neurodegenerative diseases, and several antibodies that inhibit aggregation are approved or in clinical trials to treat Alzheimer's disease. Here, we developed antibodies targeting the aggregation-prone β-propeller olfactomedin (OLF) domain of myocilin, variants of which comprise the strongest genetic link to glaucoma and cause early onset vision loss for several million individuals worldwide. Mutant myocilin aggregates intracellularly in the endoplasmic reticulum (ER).
View Article and Find Full Text PDFFront Neurol
December 2024
Department of Neurology, Leipzig University Medical Center, Leipzig, Germany.
Introduction: Modifiable risk factors play an important role in preventing dementia and reducing its progression. Regular physical activity already in midlife, which relies on intact multisensory balance control, can help to decrease the risk of dementia. However, our understanding of the relationship between postural balance and cognitive functions remains limited.
View Article and Find Full Text PDFAlzheimers Dement (Amst)
December 2024
Department of Neurology, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA.
Introduction: We investigated the feasibility and validity of the remotely-administered neuropsychological battery from the National Alzheimer's Coordinating Center Uniform Data Set (UDS T-Cog).
Methods: Two hundred twenty Penn Alzheimer's Disease Research Center participants with unimpaired cognition, mild cognitive impairment, and dementia completed the T-Cog during their annual UDS evaluation. We assessed administration feasibility and diagnostic group differences cross-sectionally across telephone versus videoconference modalities, and compared T-Cog to prior in-person UDS scores longitudinally.
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