Brain Fluid Changes Predict Alzheimer’s 10 Years in Advance

New signs of future Alzheimer’s disease have been identified by researchers at Lund University and Skane University in Sweden. Dr. Peder Buchhave and his team explain that disease-modifying treatments are more beneficial if started early, so it is essential identify Alzheimer’s disease patients as quickly as possible.

Alzheimer’s disease accounts for most cases of dementia worldwide. Its development may start up to 20 years before symptoms appear. The so-called amyloid plaques which form in the brains of people with Alzheimer’s disease contain substances known as beta-amyloid and tangles made of tau proteins.

The team followed 137 patients with mild cognitive impairment for about nine years. At the start of the study, all patients underwent lumbar puncture, in order to collect a sample of cerebrospinal fluid. During the nine years of the study, 54 percent developed Alzheimer’s disease. Sixteen percent developed other forms of dementia.

Patients’ levels of beta-amyloid 1-42, T-tau and P-tau were measured at the study’s start. Those who went on to develop Alzheimer’s disease had reduced levels of beta-amyloid 1-42 five to 10 years in advance of the disease. Raised levels of the other spinal fluids seemed to be associated with the disease, but the link occurred later on.

Findings appear in the January 2012 issue of Archives of General Psychiatry. The authors predict that:

Approximately 90 percent of patients with mild cognitive impairment and pathologic [disease-indicating] cerebrospinal fluid biomarkers will develop Alzheimer’s disease within 9.2 years. Therefore, these markers can identify individuals at high risk for future Alzheimer’s disease least five to ten years before conversion to dementia.

In conclusion, the cerebrospinal fluid levels of tau and beta-amyloid seem to be substantially altered very early in the disease process of Alzheimer’s disease.

Hopefully, new therapies that can retard or even halt progression of the disease will soon be available. Together with an early and accurate diagnosis, such therapies could be initiated before neuronal degeneration is too widespread and patients are already demented.”

They say these results support the theory that beta-amyloid metabolism is altered before the brain begins to degenerate. This may help to shape future research studies. Furthermore, once Alzheimer’s disease symptoms begin, a patient’s beta-amyloid and tau levels in their cerebrospinal fluid stay relatively constant, so might serve as markers for the efficiency of treatment, the researchers add.

But other researchers believe that, by the time the clinical symptoms of Alzheimer’s disease appear, so much neurodegeneration has occurred that disease-modifying therapy may not be effective.

This is why it is so important the underlying pathology is better understood, possibly by measuring cerebrospinal fluid levels. Experts led by Dr. Niklas Mattsson of the University of Gothenburg, Sweden, looked at this question in a large study of 750 adults with mild cognitive impairment, 529 with Alzheimer’s disease, and 304 healthy adults.
They found that, over two years, levels of beta-amyloid, T-tau, and P-tau predicted patient outcomes, suggesting that these markers “may be useful in identifying patients for clinical trials and possibly screening tests in memory clinics.”

This group of investigators has been studying these issues for several years, and their study has been described as “a tour de force” of clinical and laboratory data collections. The markers are now confirmed as being useful indicators for Alzheimer’s disease.

But Ronald C. Petersen, professor of neurology at the Mayo Clinic in Rochester, Minn., who is involved with the Study of Aging, says “it is premature to recommend application of these techniques in clinical practice.” He believes that “significant refinement of the testing procedures is necessary before these techniques can be recommended for general clinical use.”

Efforts in this direction are under way in a study based at 57 centers in the U.S. and Canada which was designed to look at biomarkers for predicting Alzheimer’s disease. A major focus of the study is to decide on standard, reliable clinical, neuroimaging and laboratory procedures.

But Prof. Petersen says, “Of critical importance, however, is what the clinician and patient will do with such results. Alzheimer disease has no treatment to prevent or alter the course of the disease, so making the diagnosis with good accuracy may aid in planning but also could be devastating news for some patients and families.

“Furthermore, false positives and false negatives occur as with any screening test. However, as biomarkers become more sophisticated, they are likely to take on an increasingly important role in the diagnosis and management of Alzheimer disease.”