Researchers at the University of Pennsylvania school of medicine say they have validated and standardized a test to determine whether a patient has Alzheimer’s disease. The test, which holds promise in the search for drugs that can halt the neurodegenerative disease, was able to detect Alzheimer’s at its earliest stages before dementia symptoms appeared and widespread irreversible damage occurred. By measuring concentrations in cerebrospinal fluid of two of the disease’s biochemical hallmarks—amyloid beta42 peptide and tau protein—the test also predicted whether a person’s mild cognitive impairment would develop into Alzheimer’s disease over time.

 

The researchers zeroed in on a biomarker found in cerebrospinal fluid that provides evidence of neuron degeneration. The researchers looked for an increase in concentration of tau proteins—and plaque deposition in the fluid, indicated by a decrease in amyloid beta42 concentration. In addition, people with two copies of the gene APOE ε4, a known risk factor for Alzheimer’s disease, had the lowest concentrations of amyloid beta42, compared to those with one or no copies.

 

“With this test, we can reliably detect and track the progression of Alzheimer’s disease,” says Leslie Shaw, co-director of the Penn Alzheimer’s Disease Neuroimaging Initiative Biomarker Core and the lead author of the study. “Validated biomarker tests will improve the focus of Alzheimer’s clinical trials, enrolling patients at earlier stages of the disease to find treatments that can at least delay—and perhaps stop—neurodegeneration. In addition, prevention trials can test methods to delay or block mild cognitive impairment from converting to full-blown Alzheimer’s.”

 

The study, published in the online edition of the Annals of Neurology, relied on cerebral spinal fluid samples contributed by 410 volunteers at 56 sites across the United States and Canada were included in this study. To independently establish threshold values for these biomarkers, cerebrospinal fluid samples from 52 Penn Memory Center volunteers with normal cognition and 56 people with confirmed Alzheimer’s disease based on post-mortem autopsy diagnosis were also measured.

 

When compared with normal, healthy adults of the same age, a pattern of changes emerged in people with mild cognitive impairment or Alzheimer’s disease. In this group, tau concentrations increased, while amyloid beta42 levels decreased as the disease progressed. The test was 87 percent accurate overall. The researchers say an accuracy of 80 percent or more is considered clinically useful.

 

In the fluid samples from those with autopsy-confirmed Alzheimer's disease, the amyloid beta42 concentration threshold was most sensitive and detected Alzheimer’s disease at a rate of 96.4 percent. The test accurately ruled out Alzheimer’s disease in 95.2 percent of the subjects. The test positively predicted the conversion from mild cognitive impairment to Alzheimer’s disease at a rate of 81.8 percent.

Further validation studies of this research test system are underway. Additional work is needed to develop additional biomarkers, as well as identify more genetic risk factors that will help distinguish Alzheimer's from other neurodegenerative diseases characterized by cognitive impairments.

 

“We have validated a test where a safe, simple lumbar puncture can provide information to confirm suspected Alzheimer's disease and predict the onset of the disease,” says John Trojanowski, director of the Penn Alzheimer's Disease Core Center. “Using this technique, we will further our understanding of how the disease progresses and what we can do to stop Alzheimer's disease before it starts.”