Scientists from Cornell are reporting in the latest issue of Annals of Neurology that they have identified 23 protein biomarkers of Alzheimer’s. The bad news? These biomarkers are in the cerebrospinal fluid, and not in blood.
“Our study is the first to use sophisticated proteomic methods to hone in on a group of cerebrospinal fluid biomarkers that are specific to autopsy-proven Alzheimer’s disease. Those postmortem tests confirmed that the panel is over 90 percent sensitive in identifying people with Alzheimer’s disease,” says Kelvin Lee, the Samuel C. and Nancy M. Fleming Professor of Molecular and Cell Biology and associate professor of chemical and biomolecular engineering at Cornell…
The Cornell study combined cutting edge “proteomics” technology, detailed image analysis, and complex computational and statistical analyses to simultaneously compare 2,000 cerebrospinal fluid proteins from 34 patients with autopsy-proven Alzheimer’s disease to those of 34 age-matched controls without the disease.
“Just as the human genome reflects the array of genes a person possesses, the ‘proteome’ is the vast collection of proteins expressed by those genes,” said Lee. “Essentially we used high-tech methods to contrast the proteomes of Alzheimer’s patients against those of a control cohort that included people with other forms of dementia as well as healthy individuals, looking for key differences between the two groups.”
This effort yielded intriguing results: 23 proteins that individually might not point to Alzheimer’s but together formed an identifying pattern or “fingerprint” specific to the illness.
“Although it need not have turned out that way, several of the 23 markers that emerged from this analysis proved to be proteins with known links to the pathological mechanisms of Alzheimer’s disease,” said Relkin. [Norman Relkin M.D. is an associate professor of clinical neurology and neuroscience at Weill Cornell –ed.]
For example, some of the biomarkers are associated with proteins that clog the brains of Alzheimer’s patients. Others molecules were linked to inflammation, also a part of Alzheimer’s brain pathology. Still other proteins in the panel were linked to synaptic dysfunction — the breakdown of communication between brain cells that occurs as Alzheimer’s disease progresses.
“A subsequent validation group of 10 patients with suspected Alzheimer’s and 18 healthy and demented control subjects turned up similar results,” said Relkin. “Based on their clinical symptoms, we found the new screen to have 93 percent sensitivity to probable cases of Alzheimer’s and a 90 percent accuracy in avoiding false diagnoses.”
Despite their excitement over the new findings, the researchers stress that the results still need to be replicated in much larger populations.