Brain scans confirm that amyloid plaque and tangles are present in the brains of people with mild cognitive impairment, a finding that will enable researchers to track and understand development of Alzheimer’s disease in real time, according to an article in the December 21 issue of the New England Journal of Medicine.

Researchers at the University of California Los Angeles used positron emission tomography (PET) imaging with a small molecule they had developed that binds to amyloid protein in the brain. Previously, only an autopsy could identify deposits and confirm a definitive diagnosis.

In the current study, researchers found that the new method was able to track disease progression over a two-year period and was more effective in differentiating patients with Alzheimer’s disease and mild cognitive impairment from normal study subjects than conventional imaging techniques.

“The study suggests that we may now have a new diagnostic tool for detecting pre-Alzheimer’s conditions to help us identify those at risk, perhaps years before symptoms become obvious,” said Dr. Gary Small, Parlow-Solomon Professor on Aging, lead study author and a professor with the Semel Institute for Neuroscience and Human Behavior at UCLA.

“This imaging technology may also allow us to test novel drug therapies and manage disease progression over time, possibly protecting the brain before damage occurs.”

The study included 83 volunteers aged 49 to 84 years. Based on cognitive testing, 25 patients had Alzheimer’s disease, 28 had mild cognitive impairment, and 30 were normal controls.

Researchers performed scans after intravenously injecting volunteers with the new chemical marker FDDNP, a molecule that binds to amyloid plaque and tangle in the brain.

Scientists found distinct differences among people with normal brain aging, patients with Alzheimer’s disease, and people with mild cognitive impairment:
The more advanced the disease, the higher the FDDNP concentration in areas where amyloid typically accumulates, the temporal, parietal and frontal lobes. Patients with Alzheimer’s disease showed the most FDDNP binding, indicating a higher level of plaques and tangles compared with amounts in other subjects.

“We could see the definitive patterns starting early in patients with mild cognitive impairment and advancing in those with Alzheimer’s disease,” said
Jorge Barrio, PhD, a coauthor and professor of medical and molecular pharmacology, David Geffen School of Medicine at UCLA.

All subjects also were scanned using the conventional chemical marker FDG, which measures metabolic function and had previously been used in aiding diagnosis of Alzheimer’s disease. In addition, 72 subjects received magnetic resonance imaging (MRI) scans.

Researchers performed follow-up scans two years later on 12 research subjects using FDDNP-PET. Patients who grew worse ? declining from normal cognitive function to mild cognitive impairment or from mild cognitive impairment to Alzheimer’s disease ? showed an increase of FDDNP binding between 5 and 11 percent compared with their previous brain scans, suggesting an increase in plaques and tangles.

A brain autopsy completed on a follow-up Alzheimer’s patient who died 14 months later showed high plaque and tangle concentrations in areas that had previously demonstrated high FDDNP binding values on the PET scan.

“This is the first time this pattern of plaque and tangle accumulation has been tracked in living humans over time in a longitudinal study,” said Small.