Researchers Develop Standard of Testing for Alzheimer’s Biomarkers

Paper in Annals of Neurology describes study that coupled beta-amyloid, tau, and APOE4 gene.

Scientists from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) report that they have confirmed the role of tau and beta-amyloid as a marker for onset of mild Alzheimer’s as well as established a method and standard of testing for these biomarkers.

Levels of beta-amyloid protein—specifically beta-amyloid 1-42— were lower among ADNI volunteers with mild cognitive impairment (MCI) compared to those with normal cognition, and lower still among those diagnosed with mild Alzheimer’s disease. The decreased levels of this biomarker in the cerebrospinal fluid may indicate that this least soluble form of amyloid is forming sticky plaques between neurons, a characteristic of Alzheimer’s.

Beta-amyloid 1-42 proved to be the most sensitive biomarker, with an overall test accuracy rate of 87% in detecting Alzheimer’s pathology in the ADNI volunteers and in people with autopsy-confirmed Alzheimer’s.

The team also found that levels of tau were higher among ADNI volunteers with MCI than among people with normal cognition, and even higher among the volunteers diagnosed with mild Alzheimer’s disease.

Additionally, the researchers factored in known genetic risk factor APOE-e4 into their analysis. The gene occurs in about 40% of all people who develop Alzheimer’s at age 65 or later. ADNI volunteers with APOE-e4, high levels of tau, and low levels of amyloid were most likely to have mild Alzheimer’s.

“Research indicates that Alzheimer’s pathology causes changes in the brain some 10 to 20 years before any symptoms appear,” says Richard J. Hodes, M.D., director of NIA, which supports ADNI. “This work gives researchers a systematic and reliable method to measure changes in cerebrospinal fluid biomarkers that may herald the onset of Alzheimer’s disease.”

The researchers collected cerebrospinal fluid from 410 ADNI volunteers at 56 different sites, tested the samples for the tau and beta-amyloid protein biomarkers associated with Alzheimer’s pathology, and then retested the volunteers a year later to track changes in cognition. The investigators also compared the ADNI cerebrospinal fluid samples to those collected from an independent group of 56 people who were later confirmed in autopsy to have had Alzheimer’s and from 52 older people with normal cognition.

The scientists noted that all 37 ADNI volunteers diagnosed with MCI at the start of the study were documented as having probable Alzheimer’s disease a year later. That conversion could be predicted by their cerebrospinal fluid biomarkers, since their baseline profiles were similar to ADNI volunteers already diagnosed with the disease.

Conversely, three ADNI volunteers with MCI at the start of the study, but whose cerebrospinal fluid biomarker levels were similar to volunteers free of the disease, reverted back to normal cognition by the end of the study.

The report appeared in the Annals of Neurology online March 17.