Genetic susceptibility to behavioural and psychological symptoms in Alzheimer disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline including loss of memory, orientation and reasoning. However, a relevant aspect of AD is the presence of a variety of behavioural and psychological symptoms in dementia (BPSD), beyond the well-known progressive cognitive impairment. Approximately 50% to 80% of patients diagnosed with AD present behavioural or psychiatric disturbances such as psychosis, depression, agitation, disinhibition, aggression, hyperactivity, and socially intrusive behaviours. These symptoms may be burdensome for physicians and caregivers and lead to earlier institutionalization and increased social and economic costs. In this view, recent literature has considered the likely genetic component of BPSD in AD, defining different clusters. Several studies have investigated whether the main recognised genetic risk factor for late-onset AD, namely the apolipoprotein E (APOE) gene, is associated with BPSD, with conflicting results. The involvement of dopamine- or serotonin-related pathways and associated genetic variabilities has been demonstrated as being interesting candidates for the neuropsychiatry manifestations of dementia. Moreover, genetic variations of neurotrophins, such as brain-derived neurotrophic factor (BDNF), have been related to depression susceptibility in AD. In the present review, we summarise the current literature on genetic risk factors to BPSD susceptibility in AD and discuss future possible treatment strategies.