RT Journal Article
T1 Peripheral expression of NPY1R-based heteroreceptor complexes reflects hippocampal neuroimmune status: Novel biomarkers for early Alzheimer’s disease detection.
A1 Moreno-Madrid, Isabel
A1 Romero-Imbroda, Jesús
A1 Reyes-Bueno, José Antonio
A1 Arrabal-Gómez, José Carlos
A1 Díaz-Casares, Amelia
A1 Díaz-Sánchez, Estela
A1 Barbancho-Fernández, Miguel Ángel
A1 Fuxe, Kjell
A1 Borroto Escuela, Dasiel Óscar
A1 Serrano-Castro, Pedro Jesús
A1 Narváez-Peláez, Manuel
K1 Alzheimer, Enfermedad de
K1 Neuropéptidos
K1 Marcadores bioquímicos
K1 Hipocampo (Cerebro)
K1 Neuroinmunología
AB Alzheimer’s disease (AD) evolves from a prodromal phase with subtle neuroimmune disturbances to overtcognitive decline and hippocampal neurodegeneration. Detecting these early changes non-invasively remains a critical unmet need. Here we show that the abundance of neuropeptide-Y receptor-type-1 (NPY1R)–based heteroreceptor complexes(NPY1R–GALR2 and NPY1R–TrkB), quantified by proximity ligation assay (PLA), constitutes a peripheral read-out of hippocampal status across two complementary rat models. In an acute AccellsiRNA model that selectively knocked down NPY1R in the cerebroventricular space (8 days post-injection), both heterocomplexes were markedly reduced in the dentate gyrus and in circulating white-blood cells (WBCs), yet hippocampal neurogenesis (doublecortin⁺ cells) and object-in-place memory were still preserved, mimicking the pre-symptomatic/mild cognitive-impairment (MCI) stage of AD. Conversely, in a bilateral olfactory bulbectomy (OBX) model that reproduces chronic AD-like pathology (2 weeks post-surgery), the same heteroreceptor complexes were diminished centrally and peripherally, and this loss co-occurred with impaired object-in-place performance and a 25 % decrease in dentate gyrus neurogenesis. These findings demonstrate that peripheral NPY1R-based heteroreceptor levels mirror hippocampal neuroimmune alterations both before and after the emergence of cognitive and neurogenic deficits. A blood-based PLA assay targeting these complexes could therefore enable ultra-early AD screening, monitor disease progression, and guide the timely initiation of disease-modifying therapies.
PB Elsevier
YR 2025
FD 2025-07-02
LK https://hdl.handle.net/10630/39895
UL https://hdl.handle.net/10630/39895
LA eng
NO Moreno-Madrid, I., Romero-Imbroda, J., Reyes-Bueno, J. A., Arrabal-Gómez, C., Díaz-Casares, A., Díaz-Sanchez, E., ... & Narváez, M. (2025). Peripheral expression of NPY1R-based heteroreceptor complexes reflects hippocampal neuroimmune status: Novel biomarkers for early Alzheimer’s disease detection. Biomedicine & Pharmacotherapy, 189, 118332
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026