A Screening Tool for Alzheimer’s Disease?
]]>Alzheimer’s disease (AD)]]> —a progressive, degenerative condition that can lead to memory loss, impaired thinking, and personality change—affects about 4 million Americans. Right now, the disease is diagnosed by a thorough medical history, cognitive evaluation, and laboratory tests to rule out other causes of ]]>dementia]]> .
Unfortunately, there is currently no way to confirm a diagnosis of Alzheimer’s disease until after death, when an autopsy of the brain can reveal damage that is characteristic of AD. Hallmarks of the disease include plaques in the brain (caused by clumping of beta-amyloid protein) and tangled filaments of a protein called tau, which traps and strangles neurons.
Scientists have known for some time that levels of beta amyloid in the cerebrospinal fluid, which constantly flows through and around the brain and spinal cord, drop in patients with AD, while levels of tau protein rise. In an article published in the April 23/30 Journal of the American Medical Association , scientists from the National Institute of Mental Health (NIMH) confirm these previous findings, and, after conducting a review of the published studies, conclude that levels of beta-amyloid and tau in the cerebrospinal fluid (CSF) may be used to diagnose Alzheimer’s patients with 89% to 92% accuracy.
About the Study
The scientists recruited 131 patients with AD and 72 controls. They performed ]]>lumbar punctures]]> (spinal taps) on all of the participants to measure levels of the proteins beta-amyloid and tau in their cerebrospinal fluid.
The researchers also analyzed the results of 51 studies involving 3133 Alzheimer’s patients and 1481 controls, which also looked at levels of beta-amyloid and tau in cerebrospinal fluid. Of these studies, 17 looked at levels of beta-amyloid, and 34 looked at levels of tau.
Analyzing levels of the two proteins in the cerebrospinal fluid of the 131 AD patients and 72 controls, NIMH scientists found a significant difference between the two groups. Beta-amyloid levels averaged 183 picograms per milliliter (pg/mL) in Alzheimer’s patients and 491 pg/mL in controls; tau levels averaged 587 pg/mL in Alzheimer’s patients and 224 pg/mL in controls. The differences were significant even after researchers controlled for age and gender. However, there was wide variation in beta-amyloid levels, with significant overlap between the groups.
Researchers were able to use these beta-amyloid and tau levels to correctly identify subjects with AD 92% of the time and correctly exclude those subjects who did no have AD 89% of the time. As far as screening tests go, these are very respectively accurate rates.
When the researchers looked at the meta-analysis, they found that 14 of the 17 beta-amyloid studies found low levels of the protein in Alzheimer’s patients compared to controls. All 34 of the tau studies found levels of the protein to be high in Alzheimer’s patients compared to controls. These patterns were true in patients with mild AD, as well as in those with moderate to severe AD.
How Does This Affect You?
While these results are compelling, their clinical application is not so clear-cut. All of the studies reported here compared CSF levels of the proteins in patients with AD to healthy controls. This comparison does not reflect the type of distinction that would normally be made in the clinic, where CSF levels of beta-amyloid and tau would be used to distinguish between patients with possible AD and patients with different types of dementia, other neurological disorders, or early cognitive impairment. Thus, additional studies must be done to see if CSF levels of beta-amyloid and tau can distinguish between these populations.
Beta-amyloid and tau levels are unlikely to be used to screen the general population for AD. Instead, it will more likely be used on people at increased risk for developing AD. Even in this population, lumbar punctures are cumbersome and unpopular among patients. A blood test would be far more desirable. In any case, additional studies will need to be done before a convenient screening tool using beta-amyloid and tau levels can be developed for Alzheimer’s disease. This would represent a major advance in the diagnosis of devastating disease that is difficult to detect in its early stages, and whose prevalence will only increase with the aging of the population.
Alzheimer’s Disease Education & Referral Center
Sunderland T, et al. Decreased B-Amyloid and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA . 2003;289:2094-2103.
Last reviewed May 2, 2003 by ]]>Richard Glickman-Simon, MD]]>
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