Chromosome 21, triplicated in Down Syndrome, contains several genes that are thought to
play a critical role in the development of AD neuropathology. The overexpression of the gene for the
amyloid precursor protein (APP), on chromosome 21, leads to early onset beta-amyloid (Aβ) plaques
in DS. In addition to Aβ accumulation, middle-aged people with DS develop neurofibrillary tangles, cerebrovascular pathology,
white matter pathology, oxidative damage, neuroinflammation and neuron loss. There is also evidence of potential
compensatory responses in DS that benefit the brain and delay the onset of dementia after there is sufficient neuropathology
for a diagnosis of AD. This review describes some of the existing literature and also highlights gaps in our knowledge
regarding AD neuropathology in DS. It will be critical in the future to develop networked brain banks with standardized
collection procedures to fully characterize the regional and temporal pathological events associated with aging in DS.
As more information is acquired regarding AD evolution in DS, there will be opportunities to develop interventions that
are age-appropriate to delay AD in DS.
Keywords: Beta-amyloid, neurofibrillary tangles, neuroinflammation, oxidative damage, posttranslational modifications, senile
plaques, trisomy 21, vascular pathology, white matter damage.
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