Unravelling monoaminergic alterations in Alzheimer's disease in Down Syndrome.

Down syndrome (DS), or trisomy 21, is the most common genetic cause of intellectual disability in humans. In addition, 50-70% of the DS individuals develops dementia due to AD before the age of 70. Studying mechanisms in DS does not only contribute to unravelling the pathophysiology in DS, but may also substantially aid to the understanding of AD. Predicting the progression of AD in DS is a major challenge in clinical practice and essential for adaptive caretaking and therapeutic interventions. We hypothesize that accurate recognition of behavioural and psychological symptoms of dementia (BPSD) may improve early identification of those at risk, and provide a non-invasive way to monitor the course to dementia. Elucidating the underlying neurobiological mechanisms further aids novel target identification for goal-directed drug development. While cognitive decline in AD cannot be prevented, specific behavioural symptoms can be reduced, thus improving the quality of life. BPSD in AD patients are diagnosed using validated questionnaires, but unfortunately, no BPSD scales are available for DS. Concentration changes in monoaminergic systems have been associated with BPSD (for example in AD). To that end, we previously quatified the levels of eight biogenic amines and their metabolites in serum of DS subjects with AD, without AD and a non-demented group that converted to AD over time. Our observations indicate that serum MHPG levels might serve a predictive biomarker for conversion to AD in DS. The major aims are therefore to (1) develop a scale for BPSD in DS, which takes DS-specific circumstances into account, (2) validate our previously reported findings on altered serum concentrations of monoaminergic neurotransmitters in relation to the status of dementia and behavioural correlates in DS, and, (3) unravel the central cause(s) of the altered monoaminergic concentrations, and MHPG in particular, in selected post mortem DS brain regions (with/without AD).

Keywords:ALZHEIMER'S DISEASE, NEUROSCIENCE, DOWN SYNDROME

Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing