Coffee is among the most commonly consumed beverage all over the world. Studies have increasingly suggested caffeine and coffee as effective therapeutic interventions against Alzheimer's disease (AD). We have therefore utilized the aluminum chloride rat model for AD to compare the influence of moderately caffeinated (Arabian) and decaffeinated (Date palm seed) coffee on cognitive impairment and pathological events in AD. AD rats given Arabian or Date palm seed coffee were protected against memory impairment and had lower serum levels of the abnormal protein (amyloid-beta; Aβ1-42), the central pathogenic contributor to AD, and transforming growth factor-beta (TGF-β). Interestingly, Date palm seed (decaffeinated) coffee seems to provide more pronounced protection against AD than Arabian (moderately caffeinated) coffee as evidenced by the greater decrease in serum Aβ levels. These results suggest a surprising therapeutic potential of moderate caffeine intake in Arabian coffee to ameliorate AD through decreasing serum Aβ levels. However, Date palm seed (decaffeinated) coffee, rich in flavonoids, appears to provide a better AD-modifying ability through a direct reduction of Aβ production. PRACTICAL APPLICATIONS: Consumption of moderately caffeinated Arabian coffee attenuated AD-induced cognitive impairment via its anti-amyloidogenic potential, decreasing Aβ levels. Moreover, intake of decaffeinated Date seed extract, rich in flavonoids, exerted a superior anti-AD potential through a direct reduction of Aβ production. Both of them were also safe and maintained hepatic and renal functions in a rat model of AlCl3 -induced AD. Further clinical studies are warranted to confirm current results and to recommend the regular drinking of Arabian coffee or Date seed extract as a protective approach to delay AD progression in vulnerable individuals or in early disease stages.