Summary: A new PET imaging study shows that Alzheimer’s disease advances faster in adults with Down syndrome, highlighting the need for tailored treatments.

Key Takeaways

  1. Adults with Down syndrome develop Alzheimer’s earlier and faster, necessitating tailored treatments.
  2. Down syndrome and genetic Alzheimer’s cases show distinct onset and progression, allowing researchers to isolate Alzheimer’s pathology from normal aging.
  3. PET scans reveal early and rapid development of tau tangles and amyloid plaques in Down syndrome, urging the need for dual-targeted therapies.


Most adults with Down syndrome will show signs of Alzheimer’s disease by middle age, a recent study by Washington University School of Medicine in St. Louis reveals. This study, published in Lancet Neurology, indicates that Alzheimer’s progresses faster in those with Down syndrome, underscoring the urgency for tailored treatments for this vulnerable group.

Early Alzheimer’s in Down Syndrome and Genetic Mutations

Historically, individuals with Down syndrome have been excluded from Alzheimer’s clinical trials, despite their dire need for such interventions. This stems from the fact that Down syndrome results from an additional chromosome 21, which carries the amyloid precursor protein (APP) gene, leading to heightened amyloid production in the brain. Consequently, cognitive decline often sets in by the age of 50.

Comparatively, individuals with autosomal dominant Alzheimer’s disease, characterized by mutations in specific genes (PSEN1, PSEN2, or APP), also face cognitive decline, typically starting in their 50s, 40s, or even 30s.

“Since these two populations develop disease at relatively young ages, they don’t have the age-associated changes seen in most Alzheimer’s patients, who are typically over age 65,” said corresponding author Julie Wisch, PhD, a senior neuroimaging engineer in Ances’ lab. “This, combined with the well-defined age of onset in both conditions, gives us a rare opportunity to separate out the effects of Alzheimer’s disease from normal aging and expand our understanding of disease pathology.”

Alzheimer’s Pathology in Down Syndrome

By studying these two populations, researchers can isolate Alzheimer’s pathology from typical age-related changes. Through PET scans, the study demonstrated that tau tangles, the second stage of Alzheimer’s, develop concurrently with amyloid plaques in Down syndrome, occurring earlier and more rapidly than in the general population.

The findings underscore the need for treatments addressing both amyloid and tau pathologies. While lecanemab targets amyloid and has FDA approval for early-stage Alzheimer’s, therapies targeting tau are also in development for later stages.

This study, part of a collaboration between the Dominantly Inherited Alzheimer Network (DIAN) and the national Alzheimer’s Biomarker Consortium-Down Syndrome (ABC-DS), sheds light on Alzheimer’s pathology, offering hope for improved diagnostics and therapies across all forms of the disease.”

Advancing Alzheimer’s Research

“This is the third paper that has come out of this longstanding collaboration between these two giant consortiums,” says co-senior author Brian A. Gordon, PhD, an assistant professor of radiology at Washington University’s Mallinckrodt Institute of Radiology and an assistant professor of psychological and brain sciences. “By studying how Alzheimer’s develops in these two unique populations, we are building a more detailed and nuanced understanding of Alzheimer’s pathology that could lead to better diagnostics and therapies for people with any form of the disease.”