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Article Abstract
Introduction: Baseline and longitudinal characteristics of cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) and plasma neurofilament light (NfL) and how they correlate interactively with neurodegeneration and cognitive decline in Alzheimer's disease (AD) are not fully understood.
Methods: We investigated dynamic changes of CSF GAP-43 and plasma NfL across different AD stages and their association with longitudinal neurodegeneration and cognitive decline up to 12 years.
Results: Individuals with hippocampal atrophy, AD-signature cortical thinning, or hypometabolism (N+) had faster plasma NfL increase rates than healthy individuals, regardless of amyloid/tau status. In contrast, none of these N+ imaging indicators correlated with more rapid increases in CSF GAP-43. Furthermore, CSF GAP-43 and plasma NfL synergistically predicted subsequent gray matter atrophy, cortical thinning, hypometabolism of the middle temporal region, and cognition.
Discussion: CSF GAP-43-associated presynaptic loss indicates tau-dependent early neurodegeneration, whereas the axonal degeneration indicated by plasma NfL is a relatively late atrophy/hypometabolism-associated fluid neurodegeneration biomarker.
Highlights: Plasma neurofilament light (NfL) was increased in N+ or cognitively impaired individuals. Increases in tau-dependent cerebrospinal fluid CSF growth-associated protein 43 (GAP-43) before imaging neurodegeneration indicators. CSF GAP-43 and plasma NfL are synergistically related to longitudinal neurodegeneration. CSF GAP-43 and plasma NfL are synergistically related to longitudinal cognitive decline.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152369 | PMC |
| http://dx.doi.org/10.1002/alz.70080 | DOI Listing |
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