Evaluation of the cannabidiol effect on the aging process of a transgenic Down syndrome model

Abstract

Down syndrome (DS) is a genetic syndrome caused by trisomy 21. The aging process in this syndrome is accelerated and the incidence of Alzheimer's disease (AD) is higher and earlier than in the population without the syndrome. Since AD is precocious in DS, it is important to study early interventions that can prevent or delay the symptomatic manifestations of dementia, as well as technologies that enable this assessment in a non-invasive way, such as the use of brain imaging techniques. Cannabidiol (CBD) will be evaluated as a treatment to reduce the neuroinflammation process present in the aging process in DS, and it will be administered for the first time in this syndrome, but it has already shown promising results as an anti-inflammatory compound in other pathologies. We hypothesize that the use of CBD will decrease the inflammatory process in animals with DS and thus delay (or prevent) memory decline in these animals. Preliminary studies from our group show that DS animals begin to show an increase in neuroinflammation during 5 months of age, progressively increasing with age until reaching a pick at 14 months of age. To test our hypothesis, we will use transgenic animals for DS, as well as transgenic animals for AD, in order to assess the effect of CBD treatment in the presence and absence of the syndrome. Positron emission tomography (PET) with [11C]PK11195 (innate immune response marker) and [18F]FDG (metabolism marker) and biofluid collections (cerebrospinal fluid and blood) will be used to enable the longitudinal assessment of the effects of treatment at different ages, as well as the object recognition test to assess short and long-term memories. Moreover, a histological evaluation will be performed through immunohistochemistry to verify the encephalic cellularity and the presence of pathological alterations associated with AD. Based on the anti-inflammatory potential of CBD and its high safe use profile - already used even in children - this experimental study has a high translational potential and could serve as a proof of principle for future clinical studies.