RT Journal Article
SR Electronic
T1 Choroid plexus APP regulates adult brain proliferation and animal behavior
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000703
DO 10.26508/lsa.202000703
VO 4
IS 11
A1 Arnaud, Karen
A1 Oliveira Moreira, Vanessa
A1 Vincent, Jean
A1 Dallerac, Glenn
A1 Dubreuil, Chantal
A1 Dupont, Edmond
A1 Richter, Max
A1 Müller, Ulrike C
A1 Rondi-Reig, Laure
A1 Prochiantz, Alain
A1 Di Nardo, Ariel A
YR 2021
UL http://www.life-science-alliance.org/content/4/11/e202000703.abstract
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.