Related Experiment Videos
Down's syndrome individuals begin life with normal levels of brain cholinergic markers
S Kish1, H Karlinsky, L Becker
1Human Brain Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Insights
Infants with Down's syndrome (DS) show normal brain cholinergic enzyme activity, suggesting intact cholinergic neurons at birth. This finding supports early intervention to prevent future Alzheimer's-like changes in DS patients.
Area of Science:
- Neuroscience
- Biochemistry
- Developmental Biology
Background:
- Down's syndrome (DS) is associated with neuropathological changes similar to Alzheimer's disease by middle age.
- A marked reduction in brain cholinergic activity is a hallmark of Alzheimer's disease and is observed in individuals with DS.
Purpose of the Study:
- To measure the activity of cholinergic marker enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in the brains of infants with DS.
- To determine if cholinergic enzyme activity is altered in early development in individuals with DS.
Main Methods:
- Autopsied brain tissue from seven infants with Down's syndrome (3 months to 1 year old) and age-matched controls were analyzed.
- Activities of ChAT and AChE were measured in various brain regions.
Main Results:
- Cholinergic enzyme activity was generally normal in all brain regions of infants with DS compared to controls.
- An exception was observed: above-normal ChAT activity in the putamen and above-normal AChE activity in the occipital cortex.
Conclusions:
- Neurochemical findings suggest that individuals with Down's syndrome are born with a normal complement of brain cholinergic neurons.
- This indicates a potential window for early therapeutic interventions to prevent the development of cholinergic deficits characteristic of Alzheimer's disease in DS.
Abstract:
We measured the activities of the cholinergic marker enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in autopsied brains of seven infants (age range 3 months to 1 year) with Down's syndrome (DS), a disorder in which virtually all individuals will develop by middle age the neuropathological changes of Alzheimer's disease accompanied by a marked brain cholinergic reduction. When compared with age-matched controls cholinergic enzyme activity was normal in all brain regions of the individuals with infant DS with the exception of above-normal activity in the putamen (ChAT) and the occipital cortex (AChE). Our neurochemical observations suggest that DS individuals begin life with a normal complement of brain cholinergic neurons. This opens the possibility of early therapeutic intervention to prevent the development of brain cholinergic changes in patients with DS.