2026-06-01T23:56:13Zhttps://riuma.uma.es/rest/oai/request
oai:riuma.uma.es:10630/398952026-02-03T11:11:17Zcom_10630_2254col_10630_37953
RIUMA. Repositorio Institucional de la Universidad de Málaga author Moreno-Madrid, Isabel author Romero-Imbroda, Jesús author Reyes-Bueno, José Antonio author Arrabal-Gómez, José Carlos author Díaz-Casares, Amelia author Díaz-Sánchez, Estela author Barbancho-Fernández, Miguel Ángel author Fuxe, Kjell author Borroto Escuela, Dasiel Óscar author Serrano-Castro, Pedro Jesús author Narváez-Peláez, Manuel 2025-09-15T08:42:32Z 2025-09-15T08:42:32Z 2025-07-02 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 https://hdl.handle.net/10630/39895 10.1016/j.biopha.2025.118332 Alzheimer’s disease (AD) evolves from a prodromal phase with subtle neuroimmune disturbances to overt cognitive 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. eng Attribution-NonCommercial-NoDerivatives 4.0 Internacional Alzheimer, Enfermedad de Neuropéptidos Marcadores bioquímicos Hipocampo (Cerebro) Neuroinmunología Peripheral expression of NPY1R-based heteroreceptor complexes reflects hippocampal neuroimmune status: Novel biomarkers for early Alzheimer’s disease detection. journal article 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 URL https://riuma.uma.es/bitstreams/bc2ebc0d-c2f5-41a6-8af3-c6986f5152c4/download File MD5 bd73e3fd74759dbf7d4e64d094b1d9f0 7581979 application/pdf Moreno-Madrid, I. et al 2025.pdf