1) The accumulation of beta-amyloid plaques and tau proteins in neurons are hallmarks of Alzheimer's disease and can trigger inflammation in astrocytes and microglia. 2) This study found that treatment with beta-amyloid increased pro-inflammatory molecules like TNF-α and IL-1β in astrocyte cultures, but treatment with cannabinoid WIN 55,212-2 increased anti-inflammatory PPAR-γ and decreased pro-inflammatory molecules, protecting cells. 3) The results suggest that beta-amyloid induces inflammation in astrocytes, a factor in Alzheimer's disease progression, and that cannabinoids may have therapeutic potential by preventing this inflammatory response.

1. INFLAMMATION IN ALZHEIMER DISEASE: EFFECTS OF
CANNABINOIDS
Diana Aguirre-Rueda and Soraya L. Valles
Department of Physiology, School of Medicine, University of Valencia, Spain.
Introduction
The hallmark in Alzheimer’s disease (AD) is both accumulation of beta-amyloid (Aβ) plates and the presence of TAU protein inside
neurons. Furthermore, glial cell activation, occurs after plates appear in brain damaged producing astrogliosis and microglia activation.
Our group has shown inflammation in astrocytes in primary culture comparing Aβ with control cells. Here we determined the action of
cannabinoids in Aβ inflammation in astrocytes in culture. Protein expression levels were detected by ELISA and Western- blot techniques
in astrocytes in primary culture treated with Aβ and/or cannabinoids. Using Aβ (10 μM) during 24 h, an increase of pro-inflammatory
mediators (TNF-α and IL-1β), compared with control astrocytes was detected. Treatment with Win 55, 212-2 (10 μM) produced increase
of anti-inflammatory mediators (PPAR-γ) and decrease of pro-inflammatory mediators, such as TNF-α and IL-1β, protecting cells to the
toxic effect of Aβ.
(C ) (Aβ) (WIN) (WIN + Aβ )
Fig. 1.- Confocal microscopy. Treated
cells for 24 h with 10 μM Aβ (40-1) (C),
10 μM Aβ (1-42) (Aβ), 10 μM WIN 55,
212-2 (WIN) and 10 μM Aβ (1-42) + 10
μM WIN 55, 212-2 (WIN+Aβ ).
Fig. 1. IL-1β levels in astrocytes in primary culture. IL-1β levels were Fig. 2. TNF-α levels in astrocytes in primary culture. TNF-α levels were
determined by ELISA in astrocytes treated for 24 h with 10 μM Aβ (40-1) determined by ELISA in astrocytes treated for 24 h with 10 μM Aβ (40-1) (C), 10
(C), 10 μM Aβ (1-42) (Aβ), 10 μM WIN 55, 212-2 (WIN) and 10 μM Aβ (1- μM Aβ (1-42) (Aβ), 10 μM WIN 55, 212-2 (WIN) and 10 μM Aβ (1-42) + 10 μM
42) + 10 μM WIN 55, 212-2 (Aβ + WIN). Data are mean ± D.S. * p < 0.05 WIN 55, 212-2 (Aβ + WIN). Data are mean ± D.S. * p < 0.05 vs control cells # p
vs control cells # p < 0,05 vs Aβ treated cells. n = 3. < 0,05 vs Aβ treated cells. n = 3.
Fig. 4. PPAR-γ expression in astrocytes in primary culture. PPAR-γ expression were
determined by western-blot in astrocytes treated for 24 h with 10 μM Aβ (40-1) (C), 10
μM Aβ (1-42) (Aβ), 10 μM WIN 55, 212-2 (WIN) and 10 μM Aβ (1-42) + 10 μM WIN 55,
212-2 (Aβ + WIN). Data are mean ± D.S. * p < 0.05 vs control cells # p < 0,05 vs Aβ
treated cells. n = 3.
CONCLUSION
These results demonstrate an unbalance between inflammatory and anti-inflammatory mediators in Alzheimer’s disease and
suggest that Aβ is able to induce inflammation in astrocytes and this effect are prevented by cannabinoids as a possible positive
effect in AD.