Crocus sativus, commonly known as saffron or Kesar, is used in Ayurveda and 
other folk medicines for various purposes as an aphrodisiac, antispasmodic, and 
expectorant. Previous evidence suggested that Crocus sativus is linked to 
improving cognitive function in Alzheimer's disease (AD) patients. The aim of 
this study was to in vitro and in vivo investigate the mechanism(s) by which 
Crocus sativus exerts its positive effect against AD. The effect of Crocus 
sativus extract on Aβ load and related toxicity was evaluated. In vitro results 
showed that Crocus sativus extract increases the tightness of a cell-based 
blood-brain barrier (BBB) model and enhances transport of Aβ. Further in vivo 
studies confirmed the effect of Crocus sativus extract (50 mg/kg/day, added to 
mice diet) on the BBB tightness and function that was associated with reduced Aβ 
load and related pathological changes in 5XFAD mice used as an AD model. Reduced 
Aβ load could be explained, at least in part, by Crocus sativus extract effect 
to enhance Aβ clearance pathways including BBB clearance, enzymatic degradation 
and ApoE clearance pathway. Furthermore, Crocus sativus extract upregulated 
synaptic proteins and reduced neuroinflammation associated with Aβ pathology in 
the brains of 5XFAD mice. Crocin, a major active constituent of Crocus sativus 
and known for its antioxidant and anti-inflammatory effect, was also tested 
separately in vivo in 5XFAD mice. Crocin (10 mg/kg/day) was able to reduce Aβ 
load but to a lesser extent when compared to Crocus sativus extract. 
Collectively, findings from this study support the positive effect of Crocus 
sativus against AD by reducing Aβ pathological manifestations.