11 Clinical Manifestations of Neuroaxonal Injury

OBJECTIVES/GOALS: The preclinical stage of Alzheimer disease (AD) is a clinically silent period that can be detected through neuroimaging and biofluid biomarkers. The goal of this study was to determine whether performance of complex daily tasks is associated with plasma biomarkers of brain amyloidosis or neuroaxonal injury in cognitively normal (CN) older adults. METHODS/STUDY POPULATION: This is a cross-sectional analysis of an ongoing longitudinal cohort study. CN older adults performed three complex daily tasks (shopping, checkbook balancing, medication management) from the Performance Assessment of Self-Care Skills in their home. Tasks were scored for independence, with more assistance required indicating worse performance. Participants had a plasma sample obtained within two years of completing the tasks. Plasma amyloid (Aβ42 and Aβ40) were evaluated by high precision immunoprecipitation mass spectrometry assays and neurofilament light (NfL) was measured with single molecule array (Simoa) assays. Nonparametric partial correlations were used to quantify the associations between task performance and plasma AD biomarkers, controlling for age and gender. RESULTS/ANTICIPATED RESULTS: 105 CN participants (mean age 74.7 years, 55% female, 88% white) were included. After controlling for age and gender, worse performance of complex daily tasks (more assistance required) was associated with increased plasma NfL (Spearman’s: 0.23, p=0.04) but not plasma Aβ42/Aβ40. DISCUSSION/SIGNIFICANCE: This study suggests that worse performance of complex daily tasks in CN older adults may be associated with increased plasma NfL a marker of neuroaxonal injury, but not with plasma amyloid. These findings could lead to a better understanding of clinical changes that may occur prior to the onset of noticeable memory symptoms in AD or related dementias.