Prolonged Tetrahydrocannabinol treatment reduces amyloid plaque deposition and restores memory function in the 5XFAD mouse model of Alzheimer’s disease

Ziel/Aim Alzheimer’s disease is the most common form of dementia with an estimated number of over 40 Million cases worldwide. While there is no cure for the disease, new therapeutic approaches are needed. As the endocannabinoid system plays a role in neuroinflammation and memory formation, it displays an interesting target for novel therapy strategies.The widely used 5XFAD mouse model of Alzheimer’s disease develops amyloid plaque pathology starting at 2 months of age accompanied by memory deficits starting at 4 months of age. Amyloid PET using ¹⁸F-Florbetaben allows an accurate in vivo detection of cerebral amyloid deposition displaying a potent tool for an early in vivo assessment of therapeutic effects.

The aim of this study was the evaluation of the effects of prolonged tetrahydrocannabinol treatment on amyloid plaque deposition and memory function in 5XFAD mice.

Methodik/Methods 5XFAD mice, that co-express five mutations of familial AD overexpressing human APP and PSEN-1, were treated with tetrahydrocannabinol for six weeks starting at the age of 5 months. Treated and untreated 5XFAD mice were scanned with ¹⁸ F-Florbetaben-PET/MRI and memory function was assessed in the Morris-Water-Maze.

Ergebnisse/Results Tetrahydrocannabinol-treated 5XFAD mice show a significantly lower ¹⁸ F-Florbetaben uptake compared to age-matched untreated 5XFAD mice. Furthermore, treated mice display improved memory function in the Morris-Water-Maze.

Schlussfolgerungen/Conclusions Tetrahydrocannabinol therapy reduces cerebral amyloid load and improves memory functions in 5XFAD mice underlining the endocannabinoid system as an interesting target for the treatment of Alzheimer’s disease.