For Dr. Ira T. Lott, Alzheimer’s disease in people with Down syndrome represents a compelling detective story, the ending of which has yet to be written.

As they age, individuals born with this genetic disorder accumulate brain plaque proteins called beta-amyloids, which are hallmarks of Alzheimer’s. Generally, by the time they’re 40, the disease has taken hold.

“But what’s unknown is why some people with Down syndrome show the behavioral symptoms of Alzheimer’s — cognitive decline and dementia — and others don’t, even though they all have the pathology of the disease,” says Lott, UC Irvine pediatrics and neurology professor.

One of only two researchers in the U.S. to receive the latest round of federal support to investigate this mystery, he’s trying to determine why — and when — cognitive impairment begins.

“Down syndrome provides an important model for Alzheimer’s disease,” he says.

Lott and his colleagues in a UCI project are enrolling 60 individuals with Down syndrome over the age of 40 who exhibit no signs of mental decline. They’ll be screened for dementia, undergo PET scans and EEG exams, and supply blood and tissue samples.

Participants will then be psychologically tested at regular intervals. In those showing deterioration of cognitive abilities, researchers will look for biomarkers that reflect these neurological changes. The idea is to establish a predictive blueprint for mental decline independent of behavioral symptoms.

“Early identification is key for intervention,” says Lott, who sees pediatric patients at UCI and CHOC Children’s hospital in Orange. “Since amyloid deposition is a lifelong process in Down syndrome, what we learn here may ultimately lead to treatments for children to lessen the cognitive deterioration as they age.”

In addition, these biomarkers could facilitate early diagnosis of age-related Alzheimer’s in all people, allowing for therapies to delay the disease’s onset.

Many people with Down syndrome, like Sandra Steigner, are glad to help researchers.

Steigner has enthusiastically participated in UCI studies related to Down syndrome for more than four years, and she has agreed to donate her brain to the tissue repository in Lott’s group for pathological examination when she dies. At 47, Steigner shows no signs of mental impairment and is enrolled in the current project.

“Sandra sees her involvement as a contribution to society,” says Elizabeth Steigner, her sister-in-law and conservator. “She does this to help children with Down syndrome — so that what Dr. Lott and others learn can improve their care someday.”

Since joining UCI in 1980, Lott has evolved into a national leader in Down syndrome neurological research. Under his guidance, the campus in 2002 conducted the first clinical trial for treating Alzheimer’s in people with Down syndrome.

His work is a valuable aspect of the Institute for Memory Impairments and Neurological Disorders (UCI MIND), the only federally recognized Alzheimer’s disease research facility with a robust program in Down syndrome.

“Dr. Lott’s achievements with Down syndrome individuals have been nothing short of amazing,” says Larry Landauer, executive director of the Regional Center of Orange County, which provides support for 17,000 people with developmental disabilities. “He inspires the families he works with. His research points to the horizon, showing us what’s possible and what can come.”