Therapeutic Potential of Cannabigerol (CBG) in Down Syndrome Associated with Alzheimer's Disease: An Experimental Model Using Ts65Dn Mice

• Grant number: 25/07583-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2025
• End date: January 31, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luiz Roberto Giorgetti de Britto
• Grantee: Polliany da Silva Mendonça
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Down syndrome (DS), caused by trisomy of chromosome 21, is the leading genetic cause of intellectual disability. This condition is associated with a high prevalence of early-onset dementia, particularly Alzheimer's disease (AD), which represents one of the main causes of mortality among adults with trisomy. The present study aims to investigate the potential therapeutic effect of cannabigerol (CBG) in Ts65Dn (3N) mice. For this purpose, trisomic (Ts65Dn - 3N) mice will receive daily intraperitoneal injections of their designated treatment (CBG or vehicle) for 30 days, starting at the 7th month of life. The animals will be monitored throughout the aging process and evaluated through behavioral assessments and PET imaging using different radiotracers ([¹¿F]FDG and [¹¹C]PK11195) at four time points: 4, 8, 12, and 18 months of age. In addition, neuroimmune alterations will be assessed by quantifying pro- and anti-inflammatory cytokines (TNF-¿, IL-1¿, IL-6, and IL-10) using the ELISA technique. Finally, immunohistochemistry will be employed to analyze microglial morphology, astrocyte density, the presence of amyloid plaques and neurofibrillary tangles, and to identify changes in choline acetyltransferase (ChAT) expression in the mouse brain. To this end, animals will be divided into three groups: A -- Ts65Dn (3N) + vehicle; B - Ts65Dn (3N) + CBG (1 mg/kg); C - Ts65Dn (3N) + CBG (10 mg/kg). Thus, this project aims to elucidate the neuroprotective effects of CBG in DS associated with AD, providing preclinical evidence to support future therapeutic strategies.Keywords: Cannabigerol; Down Syndrome; Alzheimer's Disease; Neuroinflammation. (AU)