A multitude of neuropathological studies has established a robust link between
Down syndrome and Alzheimer’s disease. Through massive projections to the entire cortex
and hippocampus, the monoaminergic-systems exert a powerful modulatory effect on brain
regions vitally important for cognition. Nevertheless, substantial evidence demonstrates
these systems are inherently vulnerable to neurodegeneration, particularly in Down
syndrome and Alzheimer’s disease. Accordingly, abnormalities in the structure and
function of subcortical monoaminergic systems constitute a common characteristic of both
disorders. Underlying these deficits are neuropathological changes in the locus coeruleus,
ventral tegmental area, substantia nigra and raphe and tuberomamillary nuclei. Fortunately,
preclinical and clinical studies suggest that pharmacotherapies targeting of these systems
may provide symptomatic relief along with disease modifying effects in Down syndrome
and Alzheimer’s disease.
Keywords: Alzheimer’s disease, dopamine, Down syndrome, histamine, locus
coeruleus, norepinephrine, raphe nuclei, serotonin, substantia nigra,
tuberomamillary nucleus, ventral tegmental area.