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Research paper
Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy
  1. Dana Wagshal1,
  2. Sethu Sankaranarayanan2,
  3. Valerie Guss2,
  4. Tracey Hall2,
  5. Flora Berisha3,
  6. Iryna Lobach1,
  7. Anna Karydas1,
  8. Lisa Voltarelli1,
  9. Carole Scherling1,
  10. Hilary Heuer1,
  11. Maria Carmela Tartaglia1,4,
  12. Zachary Miller1,
  13. Giovanni Coppola5,
  14. Michael Ahlijanian2,
  15. Holly Soares2,
  16. Joel H Kramer1,
  17. Gil D Rabinovici1,
  18. Howard J Rosen1,
  19. Bruce L Miller1,
  20. Jere Meredith2,
  21. Adam L Boxer1
  1. 1Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA
  2. 2Bristol-Myers Squibb, Wallingford, Connecticut, USA
  3. 3Kyowa Hakko Kirin Pharma, Inc., Princeton, New Jersey, USA
  4. 4Tanz Center for Research in Neurodegenerative disease, University of Toronto, Toronto, Canada
  5. 5Department of Psychiatry, Semel Institute, University of California, Los Angeles, Los Angeles, California, USA
  1. Correspondence to Dr Adam L Boxer, Sandler Neurosciences Center, Suite 190, University of California, San Francisco; Box 1207, San Francisco, CA 94158, USA; aboxer{at}memory.ucsf.edu

Abstract

Background Elevated CSF τ is considered a biomarker of neuronal injury in newly developed Alzheimer's disease (AD) and mild cognitive impairment (MCI) criteria. However, previous studies have failed to detect alterations of τ species in other primary tauopathies. We assessed CSF τ protein abnormalities in AD, a tauopathy with prominent Aβ pathology, and progressive supranuclear palsy (PSP), a primary tauopathy characterised by deposition of four microtubule-binding repeat (4R) τ with minimal Aβ pathology.

Methods 26 normal control (NC), 37 AD, and 24 patients with PSP participated in the study. AD and PSP were matched for severity using the clinical dementia rating sum of boxes (CDR-sb) scores. The INNO BIA AlzBio3 multiplex immunoassay was used to measure CSF Aβ, total τ, and ptau181. Additional, novel ELISAs targeting different N-terminal and central τ epitopes were developed to examine CSF τ components and to investigate interactions between diagnostic group, demographics and genetic variables.

Results PSP had lower CSF N-terminal and C-terminal τ concentrations than NC and AD measured with the novel τ ELISAs and the standard AlzBio3 τ and ptau assays. AD had higher total τ and ptau levels than NC and PSP. There was a gender by diagnosis interaction in AD and PSP for most τ species, with lower concentrations for male compared to female patients.

Conclusions CSF τ fragment concentrations are different in PSP compared with AD despite the presence of severe τ pathology and neuronal injury in both disorders. CSF τ concentration likely reflects multiple factors in addition to the degree of neuronal injury.

  • Alzheimer's Disease
  • CSF

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