PT  - JOURNAL ARTICLE
AU  - Arnaud, Karen
AU  - Oliveira Moreira, Vanessa
AU  - Vincent, Jean
AU  - Dallerac, Glenn
AU  - Dubreuil, Chantal
AU  - Dupont, Edmond
AU  - Richter, Max
AU  - Müller, Ulrike C
AU  - Rondi-Reig, Laure
AU  - Prochiantz, Alain
AU  - Di Nardo, Ariel A
TI  - Choroid plexus APP regulates adult brain proliferation and animal behavior
AID  - 10.26508/lsa.202000703
DP  - 2021 Nov 01
TA  - Life Science Alliance
PG  - e202000703
VI  - 4
IP  - 11
4099  - http://www.life-science-alliance.org/content/4/11/e202000703.short
4100  - http://www.life-science-alliance.org/content/4/11/e202000703.full
SO  - Life Sci. Alliance2021 Nov 01; 4
AB  - Elevated amyloid precursor protein (APP) expression in the choroid plexus suggests an important role for extracellular APP metabolites such as sAPPα in cerebrospinal fluid. Despite widespread App brain expression, we hypothesized that specifically targeting choroid plexus expression could alter animal physiology. Through various genetic and viral approaches in the adult mouse, we show that choroid plexus APP levels significantly impact proliferation in both subventricular zone and hippocampus dentate gyrus neurogenic niches. Given the role of Aβ peptides in Alzheimer disease pathogenesis, we also tested whether favoring the production of Aβ in choroid plexus could negatively affect niche functions. After AAV5-mediated long-term expression of human mutated APP specifically in the choroid plexus of adult wild-type mice, we observe reduced niche proliferation, reduced hippocampus APP expression, behavioral defects in reversal learning, and deficits in hippocampal long-term potentiation. Our findings highlight the unique role played by the choroid plexus in regulating brain function and suggest that targeting APP in choroid plexus may provide a means to improve hippocampus function and alleviate disease-related burdens.