New research indicates a connection between abnormal blood amyloid levels, linked to Alzheimer’s disease, and subtle changes in brain microstructures detectable through MRI, offering potential for earlier Alzheimer’s detection in asymptomatic individuals. The study, analyzing 128 participants with and without dementia from the 1Florida Alzheimer’s Disease Research Center, employed PET imaging to identify amyloid plaques, a key Alzheimer’s marker.

Even when a PET scan was negative for amyloid and a participant free of dementia symptoms, researchers found there was an association in those who showed abnormal amyloid levels in the blood and structural abnormalities in the brain detected through a newer method called diffusion MRI, also known as “free-water” imaging.

A team led by investigators from University of Florida’s (UF’s) Evelyn F. and William L. McKnight Brain Institute and the Norman Fixel Institute for Neurological Diseases at UF Health reported that the results represent a novel finding that free-water imaging is sensitive to early stages of decline in brain tissue and tiny structures in key parts of the brain—even when a PET scan is negative. The results were published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

“Previously people would say one of the earliest events you would see is amyloid positivity in the brain on a PET scan,” says senior author David Vaillancourt, PhD, a professor and chair of the UF College of Health & Human Performance’s department of applied physiology and kinesiology. “Our findings suggest there seem to be events occurring both in the blood and in the brain before you detect amyloid positivity in the brain.”

Blood levels of amyloid were determined using Quest AD-Detect amyloid beta 42/40, a plasma blood test developed by Quest Diagnostics to help assess risk of Alzheimer’s pathology. Collaborators from UF, the University of Miami and Mount Sinai Medical Center in Miami Beach then analyzed diffusion MRI results showing the amount of free-water, or fluid unconstrained by brain tissue.

Two main mechanisms affect free-water: atrophy, which occurs when cells are dying, and inflammation, Vaillancourt says. The new study builds upon his lab’s discovery and validation of free-water imaging as a reliable, noninvasive biomarker for another neurodegenerative malady, Parkinson’s disease.

In the new study, participants who had positive blood tests for amyloid but negative PET scans for amyloid were shown to have brain changes on diffusion MRI, including decreased cortical volume and thickness, increased free-water in 24 outer and inner parts of the brain and decreased tissue microstructure in 66 total regions, as compared to those with a negative amyloid blood test and a negative amyloid PET scan, the researchers report.

Currently, to assess patients for Alzheimer’s disease, physicians use a combination of medical history, neurological exams, cognitive and functional assessments, and additional tests that may include brain imaging, a spinal tap of cerebrospinal fluid and blood tests. Finding new methods and biomarkers to detect the disease earlier and at less expense could open the door to new clinical trials of experimental drugs to slow, prevent or treat the condition and help intervene sooner with currently available medications, Vaillancourt says.

The next step in this line of research to better correlate these findings, he says, is to follow the participants to see if those with positive amyloid blood tests become amyloid-positive on a PET scan as well as how free-water and blood change over time and how well these changes correlate with symptoms and cognitive testing and eventual clinical diagnosis of Alzheimer’s disease.

“We want to follow them over time to better understand the trajectory of change,” Vaillancourt says.