The Link between Alzheimer’s Disease and Down Syndrome. A Historical Perspective

Approximately 40–80% of persons with Down syndrome (DS) develop Alzheimer’s disease (AD)-like dementia by the fifth to sixth decade of life [1], a much younger age than is typically seen in sporadic AD. The onset of dementia symptoms in DS parallels the development of classic brain neuropathological lesions (i.e., amyloid plaques) similar to that evident in AD. Both disorders appears to have a similar genetic linkage, which is supported by the triplication of the gene that codes for amyloid beta (A4) precursor protein (APP) in persons with DS and an extra copy of the APP gene causes familial AD in persons without DS. Despite an overlap in the genetics of these disorders, the clinical presentation of dementia differs between persons with DS and AD. Whereas ‘forgetfulness’ is a typical symptom of early-phase dementia for persons in the general population, behavioral problems and personality changes are early signs of dementia for persons with DS. There are indications that amyloid burden begins in the frontal cortex before spreading to other brain regions in those with DS-AD, something that is not always the case in sporadic AD suggesting pathological variances between these disorders. These differences beg the question: Are the genetic and neuropathological commonalities found in DS- and AD-related dementia an associated similarity or do these disorders share a common pathogenesis? To address this query, the authors briefly review the clinical, histopathological, and genetic research supporting a putative link between dementia in DS and AD.

Source: Salehi, A., Ashford, J. W., & Mufson, E. J. (2016). The Link between Alzheimer's Disease and Down Syndrome. A Historical Perspective. Current Alzheimer research, 13(1), 2–6. https://doi.org/10.2174/1567205012999151021102914