Sutphen CL, Jasielec MS, Shah AR, Macy EM, Xiong C, Vlassenko AG, Benzinger TL, Stoops EE, Vanderstichele HM, Brix B, Darby HD, Vandijck ML, Ladenson JH, Morris JC, Holtzman DM, Fagan AM. Longitudinal Cerebrospinal Fluid Biomarker Changes in Preclinical Alzheimer Disease During Middle Age. JAMA Neurol. 2015 Sep;72(9):1029-42. PubMed.

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  1. This is yet another important paper from the Washington University group on the very early evolution of pathogenic processes in AD.

    We have learned a lot about AD pathogenesis by studying AD biomarkers in cross-sectional studies, often with clinical follow-up, but the key in this study is its longitudinal nature, with repeated biomarker evaluations. This may make it possible to identify when, and in what order, biomarkers change from normal, i.e., it could tell us when, during the preclinical phase, the different pathogenic processes evolve.

    Indeed, Fagan and colleagues show that CSF levels of Aβ42 (with reductions known to reflect plaque pathology) may decline as early as around 50 years of age in cognitively normal persons, and that reductions in somewhat older people (around 60 years of age) can be directly linked to brain amyloid deposition (evaluated by amyloid PET scans). Increases in neuronal markers, such as tau, come somewhat later.

    Given that we might have anti-Aβ-disease-modifying drugs in the near future, these findings are of great importance. A scenario that may not be too speculative is that these biomarkers may be used for screening purposes, with either abnormal values, or a clear change seen on  repeated sampling, used as indications of when to begin treatment. It is easy to draw parallels with other diseases where biomarkers are used for screening in middle age, such as hypercholesterolemia (serum-cholesterol) and diabetes type II (plasma-glucose).

    View all comments by Kaj Blennow

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