Biomarkers May Help Predict Risk of Alzheimer's Disease

Cerebrospinal fluid (CSF) biomarkers might aid clinicians in identifying patients with mild cognitive impairment (MCI) who may progress to Alzheimer disease (AD), according to a new study.

Researchers at the Sahlgrenska Academy (Mölndal, Sweden) conducted a multicenter study to assess the diagnostic accuracy of the CSF biomarkers β-amyloid1-42 (Aβ42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) in identifying incipient AD in a large group of patients with MCI. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited in 12 centers in Europe and the United States. Individuals with MCI were followed for at least two years or until symptoms had progressed to clinical dementia. Sensitivity, specificity, and positive and negative likelihood of the CSF markers were compared in identifying incipient AD.

The researchers found that during the follow-up period, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The researchers found that the Aβ42 assay in particular had considerable intersite variability; patients who developed AD had lower median (midpoint) Aβ42 and higher P-tau and T-tau levels than MCI patients who did not develop AD during follow-up. Cut-offs with sensitivity set at 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Aβ42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% and specificity of 72%.

"We determined in a large multicenter study that the CSF biomarkers Aβ42, T-tau, and P-tau could be used to predict with good accuracy which MCI patients will develop AD. The biomarkers may therefore be useful primarily as screening tools, selecting individuals for a detailed further clinical follow-up. Furthermore, they may be useful in enriching study populations for clinical trials of future disease-modifying AD treatments,” concluded lead author Niklas Mattsson, M.D., and colleagues. "Until such treatments become available, however, these tests are not generally appropriate for routine clinical use because it is not currently possible to alter the development of AD.”

In an accompanying editorial, Ronald Petersen, Ph.D., M.D., of the Mayo Clinic (Rochester, MN, USA) and John Trojanowski, M.D., Ph.D., of the University of Pennsylvania (Philadelphia, USA) commented that as AD has no treatment to prevent or alter the course of the disease, making the diagnosis with good accuracy may aid in planning, but also could be devastating news for some patients and families, all the more so as false positives and false negatives occur as with any screening test.

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