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January 2013

Blood-Based Biomarkers in Alzheimer Disease: Where Are We Now and Where Have We to Go?

Author Affiliations

Author Affiliation: Section for Dementia Research, Hertie Institute for Clinical Brain Research, Department of Psychiatry and Psychotherapy, and German Center for Neurodegenerative Diseases (DZNE), University of Tuebingen, Tuebingen, Germany.

JAMA Neurol. 2013;70(1):133-134. doi:10.1001/2013.jamaneurol.67

In their recent article, Doecke and colleagues1 describe the identification of a blood-based biomarker panel for classification of patients with Alzheimer disease (AD). To the strengths of this study belongs the cross-validation of the results in an independent cohort. However, there are several points that should be kept in mind when interpreting the results by Doecke et al. (1) This is the latest of a growing number of different blood-based biomarker panels with demonstrated ability to discriminate patients with AD from healthy control subjects.24 However, these panels show only in part an overlap, indicating that the perfect biomarker panel for AD diagnosis is still missing. (2) The relatively high number of 18 biomarkers in the panel bears the risk for data overfitting. (3) The specificity of the described panel should be tested by comparing patients with AD vs patients with other forms of dementia (eg, vascular dementia, Lewy body disease, and frontotemporal dementia). (4) The pathogenic relevance of the identified biomarkers should be examined by determining how the panel relates to the known AD biomarkers (cerebrospinal fluid amyloid-β and tau and/or amyloid imaging). (5) Distinguishing between patients with established AD and healthy control subjects is easy, and a marker would be of little use. On the other hand, markers of preclinical AD and/or mild cognitive impairment conversion would be of considerable use. (6) A large unmet need for the field of blood-based biomarkers to proceed to application, as has been seen in the imaging field, is the generation of standards and guidelines.

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