Does Alzheimer's progress faster in people with Down syndrome?
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A new study by researchers at Washington University School of Medicine in St. Louis discovered that Alzheimer's disease both starts earlier and moves faster in people with Down syndrome, a finding that may have important implications for the treatment and care of people with the disorder.
The findings published in the journal Lancet Neurology, compared how Alzheimer’s develops and progresses in two genetic forms of the disease: a familial form known as autosomal-dominant Alzheimer’s disease, and Down syndrome-linked Alzheimer’s.
Down syndrome is caused by the presence of an extra chromosome 21. That extra chromosome carries a copy of the APP (amyloid precursor protein) gene, meaning that people with Down syndrome produce far more amyloid deposits in their brains than is typical. Amyloid accumulation is the first step in Alzheimer’s disease. For people with Down syndrome, cognitive decline often occurs by the time they reach their 50s.
In the study, researchers mapped the development of tau tangles, the second step in the development of Alzheimer’s disease. Using PET brain scans from 137 participants with Down syndrome and 49 with autosomal dominant Alzheimer’s, the researchers examined when tau tangles appeared relative to amyloid plaques and which parts of the brain were affected.
The results revealed that amyloid plaques and tau tangles — protein abnormalities that precede cognitive decline in Alzheimer’s — accumulate in the same areas of the brain and in the same sequence in both groups. However, the process happens earlier and more quickly in people with Down syndrome, and the levels of tau are greater for a given level of amyloid.
“Normal progression with Alzheimer’s is that you see amyloid, and then you get tau — and this happens five to seven years apart — and then neurodegeneration. With Down syndrome, the amyloid and tau buildup happen at nearly the same time. Currently, no Alzheimer’s therapies are available for people with Down syndrome. Since there is a compression of the amyloid and the tau phases of the disease for people with Down syndrome-associated Alzheimer’s, we will need to target both amyloid and tau,” said corresponding author Julie Wisch, a senior neuroimaging engineer in Ances’ lab.
Reference: Julie K Wisch, PhD, Nicole S McKay, PhD, Anna H Boerwinkle, BS, James Kennedy, PhD, Shaney Flores, MS, Prof Benjamin L Handen, PhD, et al.; Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study; The Lancet Neurology; https://doi.org/10.1016/S1474-4422(24)00084-X
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