A “signature” consisting of three biomarkers in the cerebrospinal fluid was present in 90 percent of patients who had been diagnosed with Alzheimer’s disease, but also was found in more than one-third of cognitively normal older adults, according to a study in the August issue of Archives of Neurology.
Geert De Meyer, PhD, of Ghent University in Ghent, Belgium, and colleagues in the Alzheimer’s disease Neuroimaging Initiative analyzed data from 114 older adults who were cognitively normal, 200 who had mild cognitive impairment and 102 who had Alzheimer’s disease.
The cerebrospinal fluid (CSF) samples were analyzed for concentrations of beta-amyloid protein 1-42, total tau, and P-Tau181P using the xMAPplatform in which lasers excite the internal dyes. Only subjects with a valid test result for all the three biomarkers were included in the study.
De Meyer and colleagues first modeled the data from all participants, without considering their cognitive status, to identify profiles that had different levels of three biomarkers. When these profiles were applied to the data in the subgroups, the Alzheimer’s disease signature was found in 90 percent of those with Alzheimer’s disease, 72 percent of those with mild cognitive impairment and 36 percent of those who were cognitively normal.
“Results were validated on two other data sets,” the authors wrote. In one study consisting of 68 autopsy-confirmed Alzheimer’s disease cases, 94 percent were correctly classified with the Alzheimer’s disease feature. In another study with 57 patients with mild cognitive impairment who were followed up for five years, the model showed a sensitivity of 100 percent in patients progressing to Alzheimer’s disease.
The results suggest that this signature of biomarkers—developed independently of data on clinical diagnosis of Alzheimer’s disease—can correctly classify patients with the condition. “The unexpected presence of the Alzheimer’s disease signature in more than one-third of cognitively normal subjects suggests that Alzheimer’s disease pathology is active and detectable earlier than has heretofore been envisioned,” the authors concluded. “Thus, taken together, these data provide further support for the view that revision of current diagnostic criteria for Alzheimer’s disease is needed, or at least as far as early-stage Alzheimer’s disease is concerned.”
The article by De Meyer and colleagues presents a novel method of analyzing CSF biomarker data and determining how these data map onto the clinical diagnoses of Alzheimer’s disease, mild cognitive impairment and healthy control subjects, wrote A. Zara Herskovits, MD, PhD, clinical fellow in pathology of Brigham and Women’s Hospital, Boston and John H. Growdon, MD, clinical core co-Leader and founding director, Massachusetts Alzheimer's Disease Research Center and director, Memory and Movement Disorders Units, Massachusetts General Hospital, Boston, in an accompanying editorial.
“Gazing into the future when there are neuroprotective medications for Alzheimer’s disease, we can envision a recommendation that cerebrospinal fluid analyses be implemented as a screening test to identify clinically healthy individuals at risk for mild cognitive impairment and Alzheimer’s disease. The information gained would enable early application of treatments to delay onset of symptoms or slow progression of cognitive impairments,” wrote Herskovits and Growdon.