Acta Neuropathologica

, Volume 120, Issue 3, pp 385–399

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

  • William T. Hu
  • Alice Chen-Plotkin
  • Steven E. Arnold
  • Murray Grossman
  • Christopher M. Clark
  • Leslie M. Shaw
  • Leo McCluskey
  • Lauren Elman
  • Jason Karlawish
  • Howard I. Hurtig
  • Andrew Siderowf
  • Virginia M.-Y. Lee
  • Holly Soares
  • John Q. Trojanowski
Review

DOI: 10.1007/s00401-010-0723-9

Cite this article as:
Hu, W.T., Chen-Plotkin, A., Arnold, S.E. et al. Acta Neuropathol (2010) 120: 385. doi:10.1007/s00401-010-0723-9
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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.

Keywords

Biomarker Diagnosis Alzheimer’s disease Frontotemporal dementia Lewy bodies Tau Tauopathy TDP-43 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • William T. Hu
    • 1
    • 2
    • 9
  • Alice Chen-Plotkin
    • 1
    • 2
  • Steven E. Arnold
    • 3
  • Murray Grossman
    • 1
  • Christopher M. Clark
    • 4
  • Leslie M. Shaw
    • 5
  • Leo McCluskey
    • 1
  • Lauren Elman
    • 1
  • Jason Karlawish
    • 7
  • Howard I. Hurtig
    • 1
  • Andrew Siderowf
    • 1
  • Virginia M.-Y. Lee
    • 2
    • 5
    • 6
  • Holly Soares
    • 8
  • John Q. Trojanowski
    • 2
    • 5
    • 6
  1. 1.Department of NeurologyUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Center for Neurodegenerative Disease ResearchUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Department of PsychiatryUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  4. 4.Avid Radiopharmaceuticals Inc.PhiladelphiaUSA
  5. 5.Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  6. 6.Institute on AgingUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  7. 7.Department of MedicineUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  8. 8.Pfizer Global Research and DevelopmentGrotonUSA
  9. 9.Department of NeurologyEmory University School of MedicineAtlantaUSA

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