September 23, 2010
A test that measures proteins in the spinal fluid was accurate in detecting which people with memory problems would go on to develop Alzheimer’s disease. The findings could lead to a safe and accurate way to test for Alzheimer’s disease at its earliest stages, before memory loss and other symptoms become evident and when treatment may be most effective.
Experts now believe that Alzheimer’s begins 10 years or more before memory loss and thinking and personality problems become prominent. Currently, the only way to diagnose Alzheimer’s with certainty is after death, with autopsy of the brain. Still, many people continue to be diagnosed with the disease based on memory tests, brain scans and other methods.
Detecting the disease at a very early stage, before the brain has suffered a lot of damage, may mean that treatments can be developed to stop the progression of disease. Current medications for Alzheimer’s, which are typically prescribed once memory impairment becomes obvious, may ease symptoms for a time but do nothing to stop the underlying disease.
In the study, which was published in the Archives of Internal Medicine, researchers looked at 102 older men and women who met clinical criteria for Alzheimer’s. They also studied 200 with mild cognitive impairment, a form of memory loss that sometimes progresses to Alzheimer’s, and 144 who were mentally alert and free of serious memory problems.
The researchers looked at a trio of three proteins, or biomarkers, that formed a “signature” pattern in the spinal fluid, the liquid that bathes the brain and spinal cord. The three proteins are known as cerebrospinal fluid beta-amyloid protein 1-42, total CSF tau protein, and CSF phosphorylated tau 181P.
They found that the characteristic proteins were found in 90 percent of those with Alzheimer’s disease, and 72 percent of those with mild cognitive impairment. Even some of the seniors who were mentally sharp had the protein pattern: the proteins were found in 36 percent of the seniors who were still cognitively healthy.
The spinal fluid test proved remarkably effectively in predicting who would progress to Alzheimer’s disease. When they followed 57 of the patients with mild cognitive impairment for five years, they found that 100 percent of those who had the characteristic protein markers went on to develop full-blown Alzheimer’s.
The researchers suspect that many of the “healthy” seniors with the proteins in their spinal fluid would eventually also develop signs of Alzheimer’s. “The unexpected presence of the Alzheimer’s disease signature in more than one-third of cognitively normal subjects suggests that Alzheimer’s disease pathology is active and detectable earlier than has heretofore been envisioned,” they wrote.
In an editorial accompanying the study, doctors noted that, “To date, cerebrospinal fluid analyses have not been a routine component of assessment and care for patients with cognitive impairments and suspected Alzheimer’s disease in the United States. There is now ample evidence that these measurements have value; physicians need to formulate when and how to incorporate cerebrospinal fluid measurements into their practice,” they wrote.
Challenges remain. The findings must be confirmed with additional studies, and easy-to-implement versions of the test would need to be made available. The procedure requires a spinal tap, which is not currently a routine part of doctor office visits. In addition, many people who are at risk for Alzheimer’s disease may not want to know that they are very likely to develop a disease for which there is currently no effective treatment or cure.
But hundreds of drugs are under testing as possible treatments for Alzheimer’s, and some may be most effective when given at the earliest hints of the disease. “Gazing into the future, when there are neuroprotective medications for Alzheimer’s disease, we can envision a recommendation that cerebrospinal fluid analyses be implemented as a screening test to identify clinically healthy individuals at risk for mild cognitive impairment and Alzheimer’s disease,” wrote the doctors in the accompanying editorial. “The information gained would enable early application of treatments to delay onset of symptoms or slow progression of cognitive impairments.”
Gyungah Jun; Adam C. Naj; Gary W. Beecham; et al: “Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes.” Archives of Neurology, Vol. 67 (No. 8), August, 2010,
A. Zara Herskovits, MD, PhD; John H. Growdon, MD: “Sharpen That Needle” (editorial). Archives of Neurology, August 2010,.2010;67(8):918-920. doi:10.1001/archneurol.2010.151