Alzheimer’s Disease (AD) is an irreversible form of dementia that affects an estimated 4 million older Americans. Though there is no cure for AD, diagnosis in the early stages of the disease would provide patients access to existing treatments for slowing the progression of the disease. Currently, the diagnosis of AD is made by carrying out neuropsychological tests that measure memory, language skills and other brain functions, and by the exclusion of other causes of dementia, sometimes using brain scans. A definitive diagnosis can only be made at autopsy. Scientists have looked for a disease marker in the cerebrospinal fluid (CSF) that bathes the brain, but with limited success, and blood tests have not been useful at all. Two recent studies using a newer technique, proteomics, which analyzes patterns of protein abnormalities, offer hope that laboratory tests may someday be able to improve upon the imprecise clinical methods currently used to diagnose Alzheimer’s disease. Because these test procedures are complex and not yet available for wide use, it may be some time before a clinically useful version of these tests is available.

Diagnosis by CSF tests?

Researchers at Cornell University in New York reported a pattern of increased protein levels in CSF that strongly correlated with the diagnosis of Alzheimer’s disease, but were not found in other neurologic diseases. Dr. Erin Finehout and colleagues studied protein patterns in 34 persons with Alzheimer’s disease (confirmed later at autopsy) and 34 persons without AD. Their study, published in Annals of Neurology in December 2006, found increased levels of four types of proteins: those involved in transport of the amyloid protein found in Alzheimer’s disease, proteins involved in inflammation, inhibitors of enzymes that break down proteins, and proteins found in nerve cells. The pattern was found in 93% of those with Alzheimer’s disease, but in only 10% of those with other neurologic disease. These results suggest that a test may some day be available to reliably diagnose whether symptoms are due to Alzheimer’s disease or to some other disease process. Though the results from this study are promising, further research is needed.

Diagnose with a blood test?

Because the collection of CSF is difficult and not without risk, there has long been interest in trying to find a blood test that could indicate whether a person has Alzheimer’s disease or not. Researchers in the United Kingdom have now reported increased blood levels of specific proteins in more than 500 patients with AD compared with those with other forms of dementia. Professor Simon Lovestone and 19 colleagues from King’s College London, in the November 2006 issue of the journal Brain, found that complement factor H precursor (a marker of inflammation) and alpha-2 macroglobulin (an inhibitor of enzymes that break down proteins) showed the greatest increase in Alzheimer’s patients. These two proteins were then measured in blood plasma by a widely available lab technique, the Western Blot. While levels of these proteins tended to be higher in AD, they did not perform well enough to be used to make a diagnosis. Only 62% of those with AD had increases in one or both proteins, while 40% of those without AD also did. Because this was the first study to identify patterns of blood proteins that may be helpful in recognizing AD, it is likely to lead to renewed efforts to find blood tests that can help in diagnosing AD.

Sources
S1
A. Hye, S. Lynham, S. Lovestone, S. et al. Proteome-based plasma biomarkers for Alzheimer's disease. Brain (2006) 129(11):3042-3050.

S2
Finehout, E. Cerebrospinal fluid proteomic biomarkers for Alzheimer's disease. Annals of Neurology December 2006; vol 60.