Quantitation of Amyloid-Beta peptides in CSF of Alzheimer’s disease participants by immunoprecipitation/mass spectrometry (IP/MS) and solid phase extraction/mass spectrometry (SPE/MS)

2011 Pilot Project Read More


Principal Investigators: Randall Bateman, MD and Anne Fagan, PhD (WUSTL Neurology)


Alzheimer’s disease (AD) is the most common cause of dementia and is fast approaching epidemic proportions. Biomarkers of underlying disease pathology are being sought to: 1) better understand the pathophysiological processes in AD; 2) to define AD risk; and 3) to evaluate disease-modifying treatment outcomes.

Genetic, biochemical, and animal model studies strongly support the hypothesis that amyloid-beta (Aβ), the primary component of amyloid plaques in AD, plays a central role in the disease process.  Aβ exists as several isoforms that differ in amino acid length and are expressed in different ratios in the central nervous system of healthy individuals.  CSF Aβ42 is decreased by ~50% in individuals with amyloid plaques even before the onset of cognitive symptoms.  Thus, CSF Aβ42 is considered to be a very promising AD biomarker. However, current antibody-based methods for the quantification of Aβ42 differ in their reproducibility and generated values, thus making biomarker standardization efforts a top priority in the field. Furthermore, novel isoforms (Aβ15, 16, 17, 34) have recently been identified and suggest that new pathways in Aβ processing are associated with AD. The relevance of such isoform “signatures” to disease pathogenesis remains to be determined.  The current project proposes to investigate novel and sensitive mass spectometry methods of Aβ isoforms not measured with current antibody-based methods, such as Aβ15, 16, 17, 34, 38, and 43.


Patterson BW, Elbert DL, Mawuenyega KG, Kasten T, Ovod V, Ma S, Xiong C, Chott R, Yarasheski K, Sigurdson W, Zhang L, Goate A, Benzinger T, Morris JC, Holtzman D, Bateman RJ.  Age and Amyloid Effects on Human Central Nervous System Amyloid-Beta Kinetics. ANNALS of Neurology, 10.1002/ana.24454 (2015)

Updated March 2016


Hope Center Investigators

Randall Bateman

Anne Fagan


This pilot is made possible by a generous gift from Doug and Vicki Hill, and the Danforth Foundation Challenge.

Danforth Challenge