Cambridge-based collaboration reveals new insights about Alzheimer’s disease in adults with Down syndrome in upcoming Lancet publication

Almost all people with Down syndrome develop the neuropathological changes of Alzheimer’s disease by their forties but lack clinical symptoms. Dr Shahid Zaman (Consultant Psychiatrist, CPFT and Affiliated Lecturer, Dept. of Psychiatry) for the first time, in collaboration with Dr Juan Fortea at The Hospital of Sant Pau, the Catalan Foundation for Down, Barcelona, Spain describe the natural history of Alzheimer’s disease in people with Down syndrome in a publication for The Lancet.

The study shows that changes in cognitive, biochemical and imaging biomarkers of Alzheimer’s disease start more than 20 years before the onset of clinical symptoms. This long preclinical phase, in which biomarkers change following a predictable sequence, is surprisingly like that described in Alzheimer’s disease in the general population.

The order and temporality of these changes is also surprisingly similar to those described in autosomal dominant Alzheimer’s disease, a very rare hereditary form of the disease caused by mutations in some genes (including the amyloid precursor protein gene), and which also has an early onset (often before the age of 55).

The earliest changes found in the study started in adults with Down syndrome at age 30. A better understanding of this preclinical phase is essential in the development of clinical trials aimed towards preventing or moderating the progression of Alzheimer’s disease in Down syndrome.

The biomarkers described in this work could be useful for selecting therapeutic targets and for monitoring the response to a potential treatment. Clinical trials to prevent Alzheimer’s disease are essential for people with Down syndrome, and they might prove beneficial for the general population.