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Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline
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Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline
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Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline
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Journal Article
Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline
2025
Overview
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.
Publisher
John Wiley and Sons Inc
Subject
/ Alzheimer Disease - cerebrospinal fluid
/ Alzheimer Disease - diagnostic imaging
/ Alzheimer Disease - pathology
/ Biomarkers - cerebrospinal fluid
/ Cognitive Dysfunction - cerebrospinal fluid
/ Cognitive Dysfunction - diagnostic imaging
/ Cognitive Dysfunction - pathology
/ Female
/ GAP-43 Protein - cerebrospinal fluid
/ GAP‐43
/ Humans
/ Male
/ Nerve Degeneration - pathology
/ Neurofilament Proteins - blood
/ Neurofilament Proteins - cerebrospinal fluid
/ NfL
