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Association of CSF GAP-43 With the Rate of Cognitive Decline and Progression to Dementia in Amyloid-Positive Individuals.

Neurology

January 2023

From the Department of Psychiatry and Neurochemistry (A.Ö., A.L.B., N.J.A., H.K., H.Z., K.B.), Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Department of Old Age Psychiatry (N.J.A.), Institute of Psychiatry, Psychology and Neuroscience, King's College London; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A., H.Z.), London, United Kingdom; Clinical Neurochemistry Laboratory (H.K., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Fujirebio Europe NV (M.V.), Ghent, Belgium; Department of Veterans Affairs Medical Center (M.W.W.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Departments of Radiology (M.W.W.), Medicine (M.W.W.), Psychiatry (M.W.W.) and Neurology (M.W.W.), University of California, San Francisco; Department of Pathology and Laboratory Medicine (J.Q.T., L.M.S.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London, United Kingdom; UK Dementia Research Institute (H.Z.), London; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.

Article Synopsis
  • The study aimed to identify the relationship between presynaptic growth-associated protein 43 (GAP-43) levels in cerebrospinal fluid (CSF) and various Alzheimer disease (AD) biomarkers, using a retrospective analysis of the AD Neuroimaging Initiative cohort.
  • Results showed that participants with Aβ-positive status had higher GAP-43 levels regardless of cognitive impairment, and those with high levels of GAP-43 experienced worsened brain metabolism, atrophy, and cognitive decline over time.
  • Furthermore, Aβ-positive individuals with elevated GAP-43 levels were at significantly higher risk of progressing to AD dementia, indicating a potential role for GAP-43 as a predictor for AD progression.
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Medical research and clinical practice are currently being redefined by the constantly increasing amounts of multiscale patient data. New methods are needed to translate them into knowledge that is applicable in healthcare. Multiscale modeling has emerged as a way to describe systems that are the source of experimental data.

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