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Biomarker discovery for Alzheimer’s disease, frontotemporal lobar degeneration, and Parkinson’s disease

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Abstract

Ante-mortem diagnosis of neurodegenerative disorders based on clinical features alone is associated with variable sensitivity and specificity, and biomarkers can potentially improve the accuracy of clinical diagnosis. In patients suspected of having Alzheimer’s disease (AD), alterations in cerebrospinal fluid (CSF) biomarkers that reflect the neuropathologic changes of AD strongly support the diagnosis, although there is a trade-off between sensitivity and specificity due to similar changes in cognitively healthy subjects. Here, we review the current approaches in using CSF AD biomarkers (total tau, p-tau181, and Aβ42) to predict the presence of AD pathology, and our recent work using multi-analyte profiling to derive novel biomarkers for biofluid-based AD diagnosis. We also review our use of the multi-analyte profiling strategy to identify novel biomarkers that can distinguish between subtypes of frontotemporal lobar degeneration, and those at risk of developing cognitive impairment in Parkinson’s disease. Multi-analyte profiling is a powerful tool for biomarker discovery in complex neurodegenerative disorders, and analytes associated with one or more diseases may shed light on relevant biological pathways and potential targets for intervention.

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  1. William T. Hu

    Present address: Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA

Authors and Affiliations

  1. Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA

    William T. Hu, Alice Chen-Plotkin, Murray Grossman, Leo McCluskey, Lauren Elman, Howard I. Hurtig & Andrew Siderowf

  2. Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, HUP, Maloney 3rd Floor, 36th and Spruce Streets, Philadelphia, PA, 19104-4283, USA

    William T. Hu, Alice Chen-Plotkin, Virginia M.-Y. Lee & John Q. Trojanowski

  3. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Steven E. Arnold

  4. Avid Radiopharmaceuticals Inc., Philadelphia, PA, USA

    Christopher M. Clark

  5. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Leslie M. Shaw, Virginia M.-Y. Lee & John Q. Trojanowski

  6. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Virginia M.-Y. Lee & John Q. Trojanowski

  7. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Jason Karlawish

  8. Pfizer Global Research and Development, Groton, CT, USA

    Holly Soares

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  1. William T. Hu
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Hu, W.T., Chen-Plotkin, A., Arnold, S.E. et al. Biomarker discovery for Alzheimer’s disease, frontotemporal lobar degeneration, and Parkinson’s disease. Acta Neuropathol 120, 385–399 (2010). https://doi.org/10.1007/s00401-010-0723-9

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