S-022 | Altered expression of metabotropic glutamate receptor mGlu3R in brain and CSF from Alzheimer’s patients

Cellular and Molecular Neurobiology
Author: Albany Sáez | Email: albanysaez@gmail.com

Albany Sáez^1°, Eugenia Olivera^1°, Pilar Garaventa^1°,  Patricio Chrem-Méndez^2°, Ricardo Allegri^2°, Victoria Massazza^3°, María Florencia Alvarez^3°,  Horacio Martinetto^4°, Mercedes Bigi^1°, Mercedes Lasaga^1°

^1° Instituto de Investigaciones Biomédicas (INBIOMED) UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires
^2° Departamento de Neurología Cognitiva, Fleni
^3° Laboratorio de enfermedades neurodegenerativas, INEU-Fleni-CONICET
^4° Laboratorio de Biología Molecular y Bioinformática, Fleni

AD is the leading cause of dementia worldwide. The current diagnostic method includes testing biomarkers in CSF. Expanding the panel of biomarkers could improve diagnostic accuracy, which is essential for better and earlier intervention.
mGlu3R has neuroprotective and antiamyloidogenic roles. Its levels are decreased in aged PDAPP-J20 mice, which was preceded by accumulation of the isoform mGlu3Δ4. Taking this into account, our aim is to determine the association between AD and mGlu3Δ4/mGlu3R levels in the human brain/CSF.
15 controls and 15 cases were classified according to the A/T/N criteria. Aβ, Tau, mGlu3R, and Δ4 levels were determined in CSF. Neither mGlu3R nor Δ4 showed significant changes in AD patients; however, the mGlu3Δ4/mGlu3R ratio increased by 40% in AD CSF (p=0.06) suggesting a potentially relevant trend. The area under the ROC curve of this ratio was not significant (0.65, p=0.16), although Fisher’s exact test yielded an association between Δ4/mGlu3R ratio and AD (p=0.025).
These results were complemented by the analysis of 12 RNASeq databases from AD or control brains. We analyzed expression of mGlu3R and genes related to mGlu3R signaling. A significant decrease in mGlu3R, GLT1, and BDNF was observed in AD; while SRA was increased. ROC curve analysis yielded significant results for both mGlu3R (p<0.01) and the 4-gene panel (p<0.0001) as predictors for AD. In summary, mGlu3R and mGlu3Δ4 levels might be altered in AD patients and are detectable in CSF.