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.
Grants and Awards
This work has been extended to the Bateman lab’s current R01 and Zenith awards:
“A Blood Isotope Labeled Amyloid-Beta Test for Alzheimer’s Disease”
Alzheimer’s Association Zenith Award Grant (Institution Grant #3856-80569; PI, Bateman)
“CNS and Plasma Amyloid–Beta Kinetics in Alzheimer’s Disease”
NIH R01NS065667 (PI, Bateman)
Alzheimer’s disease (AD) is the most common cause of dementia and currently has no disease modifying treatments or simple accurate diagnostic tests. The goal of this project is to study how amyloid-beta (a protein thought to cause AD) is made, transported and cleared in the human body. Findings from this study may lead to better treatments for AD.
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).
Ovod V, Ramsey KN, Mawuenyega KG, Bollinger JG, Hicks T, Schneider T, Sullivan M, Paumier K, Holtzman DM, Morris JC, Benzinger T, Fagan AM, Patterson BW, Bateman RJ. Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimer’s & Dementia. 2017 Aug;13(8):841-849.
Updated January 2019