This paper comments on development of preventive therapies for dementia associated with Down’s syndrome and Alzheimer’s disease. There appears to be a common pathological role of amyloid precursor protein in the two conditions.
The idea that dementia seen in Down’s syndrome is in fact Alzheimer’s Disease is supported by several observations. Down’s syndrome is generally associated with the presence of three complete copies of chromosome 21. Alzheimer’s disease in Down’s syndrome is linked to the presence of three copies of the amyloid precursor protein (APP) gene, which resides on chromosome 21. By age 30, subjects with Down’s syndrome commonly develop amyloid plaques and neurofibrillary tangles. Up to 75% of individuals with Down’s syndrome eventually develop dementia. The apparent dependence on three copies of the APP gene was noted by the report of an elderly adult with Down’s syndrome who had a microdeletion resulting in APP disomy. There was no development of dementia or classic Alzheimer neuropathology in this case.
Additional observations include amyloid positron emission tomography (PET) imaging in individuals with Down’s syndrome. The PET data are consistent with those from non-Down’s syndrome individuals with Alzheimer’s. Amyloid plaques and tau tangles found in Down’s syndrome brain autopsy are identical to that of the general Alzheimer’s population, with their location and progression mirroring that of non-trisomic Alzheimer subjects.
The authors give a good case for testing Down’s syndrome patients to see if they could benefit from pharmacological interventions targeting sporadic Alzheimer’s.
Ness S, Rafii M, Aisen P, Krams M, Silverman W, Manji H: Down’s syndrome and Alzheimer’s disease: towards secondary prevention. Nature Reviews Drug Discovery 11(9): 655-656 (2012).