THE GLUTAMATERGIC SYSTEM IN ALZHEIMER’S DISEASE: A SYSTEMATIC REVIEW WITH META‐ANALYSIS

Glutamate is the most important excitatory neurotransmitter in the human brain, and the regulation of its homeostasis is of utmost importance for brain proper functioning. At the synapse level, glutamate binds to ionotropic (NMDAR, AMPAR and KAR) and metabotropic receptors (8 isoforms, mGluR1 to mGluR8). Also located at the glutamatergic synapse are the vesicular transporters (vGLUT), a synaptic marker, and glutamate transporters (GLT1), which are responsible for glutamate re‐uptake. Increases in the glutamate concentration in the synaptic cleft leads to a phenomenon called excitotoxicity, which causes progressive neuronal death. Nonetheless, glutamate excitotoxicity has been described as a common feature in neurodegenerative disorders, including Alzheimer’s Disease (AD). Multiple studies reported alterations in the glutamatergic system in the AD brain. Thus, considering the large number of publications, we sought to perform a systematic review with meta‐analysis to assess whether the glutamatergic system is consistently altered in AD patients.