A new tool for diagnosing Alzheimer's disease
Monitoring levels of the protein tau in cerebrospinal fluid may be a useful diagnostic tool for early detection of mild Alzheimer's disease. The recent publication of several papers on the subject, including one in the October, 1995 issue of the Annals of Neurology, point to increasing evidence that measurement of tau levels in the cerebrospinal fluid (CSF) may be useful as a screening tool, along with clinical observation, to diagnose Alzheimer's. Dr. John Q. Trojanowski, a grantee of the National Institute on Aging (NIA), and one of the authors of the Annals of Neurology paper says, "currently, autopsy material is used to confirm an Alzheimer's diagnosis. The ability to identify early Alzheimer's disease is critical to testing potential treatments for delaying the onset or for monitoring the severity of the symptoms of the disease."
In the past, Alzheimer's disease was only confirmed at autopsy. Recently however, a combination of several mental ability tests and advanced neurological scanning methods have given doctors much better diagnostic tools for studying Alzheimer's in living patients. Earlier this year, scientists reported on the possible use of Positron Emission Tomography (PET) to diagnose Alzheimer's up to 20 years prior to the appearance of outward symptoms in people at risk because of a family history of the disease.
The key to Dr. Trojanowski and colleagues' discovery is the speculation that a protein called tau is a major building block for the brain tangles found in Alzheimer's patients. It is theorized that the tau protein in Alzheimer's patients becomes attached to a form of phosphorous and eventually becomes incorporated into tangles. These tau tangles, one of the hallmarks of Alzheimer's disease found in all autopsied brains, became an obvious marker for researchers to investigate. Based on this theory, scientists in Germany recently demonstrated that higher levels of tau in CSF correlated with higher degrees of dementia in Alzheimer's patients. These results now have been corroborated by scientists in Japan, Sweden, and the United States.
The study Dr. Trojanowski worked on was led by Dr. Hiroyuki Arai and funded, in part, by the NIA. The study looked at 70 Alzheimer's patients ranging in age from their sixties to their eighties, 96 patients of various ages with other neurological disorders, and 19 normal subjects. After collecting CSF by a lumbar puncture, investigators in this and other studies determined tau levels by a variety of measures. The results were remarkably consistent across ethnicity, nationality, and testing method. Alzheimer's patients had increased tau levels at the earliest stages of the disease when compared to controls and patients with other neurological diseases.
Most interestingly, levels of tau did not increase or change as patients advanced to later stages of Alzheimer's disease, suggesting to Dr. Trojanowski that Alzheimer's patients' tau reaches a critical level very early in the disease process. The fact that the tau level is high early in the disease process makes tau particularly intriguing as an early marker for Alzheimer's. The tau finding also suggests to researchers that Alzheimer's may start at a cellular level, with tau providing a molecular marker within the cell for the disease.
Additionally, tau levels were not significantly different in patients who got Alzheimer's early in life (before age 65) versus those who got it later, or for those who had a genetic predisposition to Alzheimer's associated with their ApoE gene status. This leads the investigators to suggest that tau may be a more consistent marker for Alzheimer's disease than genetic testing or other methods.
As with many exciting discoveries, this finding is a first step in a process that needs further corroboration and refinement. In particular, Dr. Trojanowski and his fellow scientists are searching to find out if there are unique forms of tau which may be signatures of the Alzheimer's disease process. This tau testing, which will probably be useful in conjunction with some of the other tests for Alzheimer's, is not currently available, or advisable, for people who are concerned that they may be predisposed towards Alzheimer's disease. There is only one drug approved for treatment of Alzheimer's and it is of short-term and limited usefulness. Until drugs that can intervene in abnormal tau formation along with more sensitive testing methods are developed, current tau tests are chiefly useful to scientists in research settings.
This finding is important because it gives researchers another tool for developing drugs to intervene early in the Alzheimer's disease process. Working with Dr. Trojanowski in his NIA-supported Alzheimer's Disease Center at the University of Pennsylvania School of Medicine in Philadelphia, and at four research centers in Japan were Drs. Hiroyuki Arai, Masanori Terajima, Masakazu Miura, Susumu Higuchi, Taro Muramatsu, Nobuo Machida, Hisatomo Seki, Sadao Takase, Christopher M. Clark, Virginia M.-Y. Lee, and Hidetada Sasaki.
The National Institute on Aging, part of the National Institutes of Health, leads the Federal effort supporting basic, clinical, epidemiological, and social research on Alzheimer's disease, aging, and the special needs of older people.