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ON THE COVER: Alzheimer’s brain. Amyloid plaques accumulate in the brains of Alzheimer patients (left), but not in unaffected brains (right). Clinical studies have provided evidence that cerebrospinal fluid (CSF) amyloid-β1-42 and tau proteins are reliable biochemical markers of Alzheimer disease neuropathology. Newly revised criteria for the diagnosis of Alzheimer disease include CSF biomarkers for use in research settings. The selection of Alzheimer disease patients at the predementia stage by use of CSF biomarkers may also improve the statistical power of clinical trial design. In this issue of Clinical Chemistry, Shaw and colleagues provide a comprehensive review of the clinical utility and analytical challenges in the measurement of cerebrospinal fluid amyloid-β1-42 and τ proteins as Alzheimer disease biomarkers. These authors discuss the sources of analytical variability and global efforts to overcome the challenges of advancing the use of immunoassays for measuring amyloid-β1-42 and τ proteins, the association of CSF biomarkers with imaging biomarkers and genetic factors, and the clinical utility of immunoassay-based Aβ and τ protein measurements for early diagnosis and predicting disease progression. ©Science Source. Reproduced with permission.