THURSDAY, April 18, 2024 (HealthDay News) -- Doctors have long known that nearly all people with Down syndrome will go on to develop Alzheimer's disease in later life; the two conditions are genetically connected.
Now, new research shows that Alzheimer's also begins earlier and progresses faster in these individuals, striking many in middle age.
The finding highlights how urgently research into the Down-Alzheimer's connection is needed, said study co-senior author Dr. Beau Ances.
“Currently, no Alzheimer’s therapies are available for people with Down syndrome,” said Ances, a professor of neurology at Washington University in St. Louis.
Ances treats patients with Down syndrome, and he noted that such patients are often excluded from Alzheimer’s clinical trials.
“This is a tragedy because people with Down syndrome need these therapies as much as anyone,” he said in a university news release.
Down syndrome is caused by the presence of an additional chromosome 21. This extra chromosome also brings with it an extra copy of the APP (amyloid precursor protein) gene -- meaning that the amyloid protein brain deposits that are a hallmark of Alzheimer's disease pile up more rapidly in people with Down syndrome.
That means that for individuals with Down syndrome, Alzheimer's can often begin before the age of 50.
The study also focused on another set of people with early-onset Alzheimer's disease: Those with an inherited form of the illness called autosomal-dominant Alzheimer’s disease.
Because these individuals inherit a mutated form of one of three genes -- PSEN1, PSEN2 or APP -- they too can develop Alzheimer's as early as their 30s or 40s, the study authors explained.
In their research, Ances' group looked at the accumulation in patients' brains of a second type of Alzheimer's-linked protein, called tau "tangles".
They took brain scans of 137 participants with Down syndrome and 49 with autosomal dominant Alzheimer’s, and found that amyloid plaques and tau tangles gather in roughly the same brain areas and along similar timelines.
However, compared to folks with autosomal-dominant Alzheimer's, tau accumulation began earlier in the brains of Down syndrome patients, and it also happened at a greater rate in relation to amyloid buildup.
“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,” explained study corresponding author Julie Wisch, a senior neuroimaging engineer in Ances’ lab. “With Down syndrome, the amyloid and tau buildup happen at nearly the same time.”
The study was published April 15 in The Lancet Neurology journal.
Right now there's only one drug, lecanemab (Leqembi) approved for Alzheimer's disease, and it targets amyloid buildup in the early stages of the illness.
“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,” Ances said. “We may need to come up with different approaches for this population.”
More information
Find out more about connections between Down syndrome and Alzheimer's disease at the Alzheimer's Association.
SOURCE: Washington University news release, April 15, 2024
