Over thelast decades, EAAT2 loss/dysfunction in AD, the most common causeof dementia, became a potential target for pharmacological intervention.Here, we briefly discuss immunohistochemical reports from post-mortemhuman brains and experimental models showing that EAAT2 dysfunction/lossand glutamatergic excitotoxicity may precede neurodegeneration andclinical manifestations in the AD continuum. The gene discussed is SLC1A2; the disease is Alzheimer disease.