From the Doctor's Desk: New Biomarker May Help with Early Diagnosis of Alzheimer's Disease

June 28, 2011

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By Daniel C. Potts, MD
Tuscaloosa, Alabama

Every day in my practice I see both patients and relatives of patients who are concerned about their chances for developing Alzheimer's disease. Some of them are offspring of affected individuals and some are people with mild cognitive impairment. Fortunately, there are developments in the area of biomarkers that may help answer their questions.

A biomarker is the name given to a biologic substance (usually a protein) which serves as an indicator for a particular disease. Biomarkers can predict initial pathologic changes in the development of various disease states, and, in doing so, may offer tools for early detection and treatment.

Over the past few years several new biomarkers have been identified which may help to predict the later development of Alzheimer's disease. For example, reduced concentrations of Aβ1-42 and increased concentrations of tau in the cerebrospinal fluid (CSF) have been shown to fairly reliably predict the later development of Alzheimer's disease.

In Neurology® 2011;77:35–38, authors Perneczky and Tsolakidou, et al, identify a new biomarker, sAPPβ, which is produced earlier in the development of Alzheimer pathology than most other substances. In a group of 58 persons with Mild Cognitive Impairment (MCI) (pre-dementia), CSF sAPPβ concentrations were significantly higher in those individuals who went on to develop Alzheimer's disease than they were in frontotemporal dementia patients, or in those whose MCI did not progress. When combined with MRI measurements of hippocampal atrophy (shrinkage of the part of the brain involved in short-term memory) and tau concentration (a marker of neuronal injury and degeneration), increased concentrations of sAPPβ in the CSF of individuals with MCI strongly predicts the later development of Alzheimer's disease.

Indeed, it appears that sAPPβ may more effectively identify early Alzheimer's disease than Aβ1-42 , currently the most accepted and utilized biomarker. This may have to do with the fact that sAPPβ is generated earlier in the development of Alzheimer's disease, and may mark one of the first byproducts in this chain of events. Assessing tau concentrations and performing a brain MRI with hippocampal measurements further enhances the predictive potential of this biomarker.

Developments like those described above are especially exciting to those with relatives who have Alzheimer's disease, and to all of us who have been touched closely by it. And the implications are potentially even more exciting! Often the identification of biomarkers heralds a time of enlightened developments in effective treatment. Though no cure has emerged to date, the elusive pieces of this puzzle called Alzheimer's disease are falling into place.

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