Down syndrome (DS) is a genetic disorder caused by full or partial triplication of chromosome 21 (HSA21). Key genes related to Alzheimer’s disease (AD) pathology reside on HSA21, causing lower life expectancy due to dementia. Triplication of the amyloid precursor protein gene is associated with rapid accumulation of amyloid beta, one neuropathological feature of AD. Accumulation of amyloid beta promotes neurofibrillary tangle accumulation in the brain, the other feature of AD neuropathology. While virtually all individuals with DS have significant AD neuropathology by age 40, a clinical diagnosis for dementia is generally not made until the age of 55. This gap between accumulating neuropathology and clinical symptomatology represents a period of minimal or subtle symptoms not detectible by current clinical measures. Recent research has demonstrated possible contributions of cerebrovascular disease and possible early markers of prodromal disease. Improved diagnostic accuracy and earlier diagnosis are critical for developing future research and clinical trials to address AD in Down syndrome.
Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Sixth Edition), Volume 1, 2020, Pages 283-297,