Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease

  1. Dimitra G. Georganopoulou*,
  2. Lei Chang,
  3. Jwa-Min Nam*,
  4. C. Shad Thaxton*,
  5. Elliott J. Mufson,
  6. William L. Klein,§,, and
  7. Chad A. Mirkin*,,
  1. *Department of Chemistry and Institute of Nanotechnology and Department of Neurobiology and Physiology, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208; and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612
  1. Communicated by M. Frederick Hawthorne**, University of California, Los Angeles, CA, December 16, 2004 (received for review September 29, 2004)

Abstract

The recently developed ultrasensitive bio-barcode assay was used to measure the concentration of amyloid-β-derived diffusible ligands (ADDLs), a potential soluble pathogenic Alzheimer's disease (AD) marker, in the cerebrospinal fluid (CSF) of 30 individuals. ADDL concentrations for the subjects diagnosed with AD were consistently higher than the levels in the CSF taken from nondemented age-matched controls. Studies of ADDLs or for any other potential pathogenic AD markers in CSF have not been possible because of their low concentration in CSF (<1 pM). This study is a step toward a diagnostic tool, based on soluble pathogenic markers for the debilitating disease.

Footnotes

  • To whom correspondence may be addressed. E-mail: camirkin{at}chem.northwestern.edu or wklein{at}northwestern.edu.

  • § W.L.K. is a cofounder and member of the Scientific Advisory Board of Acumen Pharmaceuticals, Inc.

  • C.A.M. is a founder of Nanosphere, Inc.

  • Author contributions: D.G.G., L.C., W.L.K., and C.A.M. designed research; D.G.G., L.C., J.-M.N., and C.S.T. performed research; D.G.G., L.C., W.L.K., and C.A.M. analyzed data; E.J.M., C.A.M., and W.L.K. contributed new reagents/analytic tools; and C.A.M. wrote the paper.

  • Abbreviations: AD, Alzheimer's disease; ADDL, amyloid-β-derived diffusible ligand; pAb, polyclonal Ab; CSF, cerebrospinal fluid; NP, nanoparticle; MMP, magnetic microparticle.

  • See Commentary on page 2263.

  • ** M.F.H. is a member of the scientific advisory board of Lexrite Labs.

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