Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders
Year: 2024
Type: review
Study design: Observational Study
Abstract: The direct causes of neurodegeneration underlying Alzheimer’s disease (AD) and many other dementias, are not known. Here we identify serum amyloid P component (SAP), a constitutive plasma protein normally excluded from the brain, as a potential drug target. After meta-analysis of three genome-wide association studies, comprising 44,288 participants, cis -Mendelian randomization showed that genes responsible for higher plasma SAP values are significantly associated with AD, Lewy body dementia and plasma tau concentration. These genetic findings are consistent with experimental evidence of SAP neurotoxicity and the strong, independent association of neocortex SAP content with dementia at death. Depletion of SAP from the blood and from the brain, as is provided by the safe, well tolerated, experimental drug, miridesap, may therefore contribute to treatment of neurodegeneration.
Source: Open Biology
DOI: 10.1098/rsob.230419
Institutions: Utrecht University, Amsterdam UMC Location University of Amsterdam, University Medical Center Utrecht, British Heart Foundation, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University College London, University of Amsterdam, The Royal Free Hospital, UCL Queen Square Institute of Neurology
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,839
Funders: Government of the United Kingdom, UK Research and Innovation, National Institute for Health and Care Research, British Heart Foundation, University College London, University College London Hospitals NHS Foundation Trust, National Institutes of Health, HORIZON EUROPE Framework Programme, U.S. National Library of Medicine
Awards: Predicting patient relevant outcomes in people with diabetes through integration of electronic healthcare records, genomics and machine learning, Accelerator Award, G500343079, Bioinformatics Strategies for Genome Wide Association Studies, Evaluating combination therapeutics for CVD prevention using Mendelian randomisation and phenome-wide scans, G6543613632, G6814491137, G8264949757
OpenAlex ID: W4400672758