Alzheimer's may progress faster in people with Down syndrome

A new study showed that the Alzheimer's may begin early and progress more quickly in people with Down's syndrome . The findings, published in the scientific journal Lancet Neurology on the 15th, may have important implications for the treatment and care of this vulnerable group of patients.

O study 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 Alzheimer's disease linked to Down syndrome.

For Beau Ances, professor at Daniel J. Brennan Neurology and co-senior author of the study, the findings are important because “currently, no Alzheimer’s therapy is available for people with Down syndrome.” “This is a tragedy because people with Down syndrome need these therapies as much as anyone else,” says Ances, in a press release.

Link between Alzheimer's and Down syndrome

Down syndrome is a genetic disorder characterized by the presence of an extra chromosome 21. This chromosome carries a copy of the APP (amyloid precursor protein) gene, which causes people with this syndrome to produce many more amyloid deposits in their brains than normal.

Previous studies have shown that amyloid accumulation is one of the main causes of Alzheimer's disease. For people with Down Syndrome, the cognitive decline characteristic of the disease generally occurs at age 50.

People with autosomal dominant Alzheimer's disease also have a schedule that can increase the chances of cognitive decline. These people inherit mutations in one of three specific genes: PSEN1, PSEN2, or APP. They tend to develop cognitive symptoms at the same age as their parents: in their 50s, 40s or even 30s.

“Because these two populations develop the disease at relatively young ages, they do not show the age-associated changes seen in most Alzheimer's patients, who are typically older than 65,” says study corresponding author Julie Wisch, senior engineer. of neuroimaging in the Ances laboratory. “This, combined with the well-defined age of onset in both conditions, gives us a rare opportunity to separate the effects of Alzheimer's disease from normal aging and expand our understanding of the disease's pathology.”

How was the study carried out?

For the study, researchers mapped the development of tau tangles, another risk marker for developing Alzheimer's. They performed positron emission tomography (PET) scans of the brains of 137 participants with Down syndrome and 49 with autosomal dominant Alzheimer's disease. This made it possible to examine when tau tangles appeared in relation to amyloid plaques and which parts of the brain were affected.

The study showed that amyloid plaques and tau tangles accumulate in the same areas of the brain and in the same sequence in both groups. However, the process starts earlier and is faster in people with Down syndrome. Additionally, tau levels are higher for a given amyloid level.

“The normal progression of Alzheimer's is that you see amyloid and then tau — and that happens five to seven years apart — and then neurodegeneration,” Wisch explained. “With Down syndrome, the accumulation of amyloid and tau occurs at almost the same time.”

Currently, there is only one FDA-approved treatment for Alzheimer's disease (Food and Drug Administration), regulatory agency in the United States, and which has been proven to alter the course of the disease: lecanemab, which targets amyloid.

Because amyloid accumulation is the first step in the disease, lecanemab is recommended for people in the early stages of Alzheimer's disease with mild symptoms. Tau-targeted therapies are also in development, aimed at people in later stages of the disease, when tau pathology plays a more prominent role.

“Because there is a compression of the amyloid and tau phases of the disease in people with Alzheimer's associated with Down syndrome, we will need to target both amyloid and tau,” Ances said. “We may need to find different approaches for this population.”