Hippocampal volume moderates the association between cerebrospinal fluid growth-associated protein 43 and episodic memory performance in older adults

This study examined the relationships between fluid and imaging biomarkers associated with memory (cerebrospinal fluid growth-associated protein 43 [CSF GAP-43] and hippocampal volume) and episodic memory performance in 586 older adults (mean age = 72.6 years, SD = 7.2) from the Alzheimer's Disease Neuroimaging Initiative who completed CSF collection, Magnetic Resonance Imaging, and neuropsychological testing. Hierarchical linear regressions assessed whether FreeSurfer-derived total hippocampal volume or hippocampal subfield volume (subiculum, presubiculum, dentate gyrus, CA1) moderated the association between GAP-43 and episodic memory performance. GAP-43 and hippocampal volume were independently associated with episodic memory performance. Greater GAP-43 was associated with lower episodic memory performance in older adults with average or below-average (-1 SD) total and subfield (subiculum, presubiculum, dentate gyrus) hippocampal volume. No associations were observed in participants with above-average (+1 SD) volume. These findings suggest that GAP-43 may serve as a biomarker correlate of episodic memory impairment in those with average or below-average hippocampal volume.