Abstract
BACKGROUND: The relationship and mechanisms between body mass index (BMI) and cognition are complex and inconclusive. Additionally, the role of neuronal calcium dysfunction, reflected by cerebrospinal fluid (CSF) Visinin-like protein 1 (VILIP-1), in the mechanisms linked with BMI and Alzheimer's disease (AD) has not been investigated. OBJECTIVE: To investigate the relationship between CSF VILIP-1, BMI, and AD pathologies in non-demented elderly at early stages of AD. METHODS: Baseline CSF AD core biomarkers (amyloid-β(42) [Aβ(42)], phosphorylated tau [P-tau], and total tau [T-tau]) were measured for 1201 non-demented participants, selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, among whom 128 had measurements of CSF VILIP-1. Multivariate linear regression, causal mediation analyses, and linear mixed effects models were conducted to detect these associations. RESULTS: The average age of participants was 72.6. CSF VILIP-1 was decreased in A+/TN- (A-positive/T- and N- negative) group and elevated in A-/TN + (A-negative/T- or N-positive) and A+/TN + groups, as compared with A-/TN- group. In total participants, BMI was negatively related to CSF P-tau, T-tau, P-tau/Aβ(42) and T-tau/Aβ(42). Noticeable associations were also presented between CSF VILIP-1 and AD core biomarkers, but not with Aβ(42) after stratification by A/T/N scheme. Furthermore, the influences of BMI on CSF tau pathology were mediated by CSF VILIP-1. Higher baseline CSF VILIP-1 correspond to faster longitudinal cognitive decline. CONCLUSIONS: Our findings indicated that CSF VILIP-1 changed dynamically and might be a key mediator in the associations between BMI and tau pathology, providing new insights into understanding the mechanisms underlying BMI-related cognitive deficits in non-demented elderly.