A-88: DOPA Decarboxylase Relates to Hippocampal Atrophy and Amplifies Tau-Associated Memory Dysfunction in Older Women at Risk for Alzheimer’s Disease

Abstract

Objective: Cerebrospinal fluid (CSF)-derived DOPA decarboxylase (DDC) is a promising biomarker of synucleinopathy; however, its relevance in Alzheimer’s disease (AD)-risk cohorts remains unclear. Research suggests that DDC may index co-pathology contributing to neurodegeneration and memory dysfunction beyond AD pathology. We tested the independent and interactive effects of higher CSF DDC and tau burden on hippocampal volume and memory in 52 older women (Mage=72.3, SD=4.2) at risk for AD. Method/Data Selection: CSF DDC was quantified via the Alamar NULISAseq CNS Disease Panel. Amyloid (Aβ) positivity was derived from CSF Aβ42/40. Tau burden was measured using an 18F-MK6240 tau-PET meta-temporal composite SUVR. Hippocampal volume was derived from 3.0T MRI. Episodic memory was indexed by a composite of delayed recall scores. Regression models adjusted for age, APOE-ε4, Aβ positivity, and tau-PET, plus total intracranial volume for hippocampal volume and quality of education (WRAT4 Word Reading) for memory. Results/Data Synthesis: Higher DDC was associated with smaller hippocampal volume after adjusting for Aβ positivity and tau-PET (β=-.27, p=.036). Neither Aβ positivity nor tau-PET was significantly associated with hippocampal volume, and the DDC*tau-PET interaction was not significant, suggesting an independent relationship. In contrast, DDC moderated the association between tau-PET and memory (β=-5.15, p=.007), indicating a synergistic effect of higher DDC and greater tau burden on memory dysfunction. Conclusions: Higher DDC was associated with reduced hippocampal volume and amplified the negative association between tau and memory, consistent with a mixed-pathology model in which co-pathology worsens the clinical expression of AD. Results support further investigation of DDC as a candidate biomarker of co-pathology in preclinical and prodromal AD.