Age-related molecular and functional remodeling of the choroid plexus in the mouse lemur

Aging is accompanied by complex alterations in brain structure and functions, with growing evidence implicating the choroid plexus (CP) as a key regulator of cognitive and motor function. Here, we investigated age-related changes in the CP of the gray mouse lemur (Microcebus murinus), a non-human primate model that recapitulates human brain aging features. Lemurs of different ages underwent behavioral testing, followed by transcriptomic profiling and immunofluorescence analyses of lateral ventricle CP tissue. Behavioral assessments revealed age-related declines in motor coordination and exploratory drive, whereas working memory and visual discrimination remained largely preserved. Histological analysis showed no significant structural alterations in CP architecture. Transcriptomic profiling identified 1,519 upregulated and 1,682 downregulated genes with aging, highlighting increased interindividual heterogeneity, upregulation of immune- and transport-related pathways, and downregulation of signaling and intercellular communication processes. Functionally, AQP1 protein expression decreased with age without changes in mRNA levels, suggesting post-transcriptional regulation, whereas NKCC1 and TTR expression were largely maintained. Notably, reduced AQP1 expression correlated with age-related motor decline. These findings indicate that CP aging in the mouse lemur is characterized by selective functional vulnerability, immune activation, and transcriptional remodeling, yet essential barrier and secretory functions are largely preserved. Our results highlight a primate-like aging profile of the CP, providing insights into mechanisms by which CP dysfunction may contribute to age-related motor decline and altered brain homeostasis. Overall design: RNA-seq profiling of the choroid plexus extracted from gray mouse lemurs of different age groups (young: Y; adult: A; old: O).