# Association of APOC1 with cortical atrophy during conversion to Alzheimer’s disease

## TL;DR

This study explores how APOC1 gene expression is linked to brain changes in Alzheimer's disease progression, suggesting it could be a new target for research.

## Contribution

The study identifies APOC1 as a novel genetic factor associated with cortical thinning and faster conversion to Alzheimer’s disease.

## Key findings

- High APOC1 expression correlates with faster conversion to Alzheimer’s disease in patients with mild cognitive impairment.
- APOC1 expression is significantly associated with cortical thickness changes in paralimbic brain regions.
- Mediation analysis suggests APOC1 may influence memory via cortical thickness changes.

## Abstract

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder, with its progression influenced by aberrant gene expression and alterations in the brain network topology. Although APOE has been extensively studied in relation to AD, the role of APOC1 remains relatively underexplored. This study investigated the impact of APOC1 on changes in cortical thickness (CTh) during conversion to AD in a longitudinal setting. Using a normative modeling approach, we examined changes in CTh in patients with mild cognitive impairment (MCI). The spatial patterns of CTh changes were then correlated with APOC1 mRNA expression levels. We estimated the time to conversion to AD and compared progression rates between the low and high APOC1 expression groups. Finally, mediation analysis was performed to assess the indirect effects of APOC1 expression on memory function via CTh changes. In patients with MCI and AD, reduced CTh was observed in the limbic and default mode regions, with a notable impact on the entorhinal cortex, parahippocampus, and fusiform gyrus when comparing baseline and follow-up measurements. The degree of change in CTh was significantly associated with APOC1 expression, with the paralimbic regions identified as particularly vulnerable. Furthermore, the high APOC1 expression group demonstrated more rapid conversion to AD than that observed in the low expression group. Mediation analysis indicated a trend suggesting that APOC1 expression indirectly affected memory and cognitive function through its influence on CTh. These results highlight the potential of APOC1 as an additional focus of AD research, offering insights into the genetic influences on AD pathology.

The online version contains supplementary material available at 10.1007/s11357-025-01695-6.