Document Type
Journal Article
Publisher
Nature Publishing Group
School
Centre of Excellence for Alzheimer’s Disease Research and Care / School of Medical Sciences
RAS ID
21905
Funders
Australian National Health and Medical Research Council Program Grant 350833
Australian Research Council Discovery Project Grant DP120102078
Medical Research Foundation.
Grant Number
NHMRC Number: 350833, ARC Number : DP120102078
Abstract
The autosomal dominant form of Alzheimer's disease (ADAD) is far less prevalent than late onset Alzheimer's disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose metabolism. Fewer changes were observed at the asymptomatic than symptomatic stage with seven and 16 proteins altered significantly in aMC and sMC, respectively. This included complement components C3, C5, C6, apolipoproteins A-I, A-IV, C-I and M, histidine-rich glycoprotein, heparin cofactor II and attractin, which are involved in inflammation, lipid metabolism and vascular health. Proteins involved in lipid metabolism differed only at the symptomatic stage, whereas changes in inflammation and vascular health were evident at asymptomatic and symptomatic stages. Due to increasing evidence supporting the usefulness of ADAD as a model for LOAD, these proteins warrant further investigation into their potential association with early stages of LOAD.
DOI
10.1038/srep29078
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Muenchhoff, J., Poljak, A., Thalamuthu, A., Gupta, V. B., Chatterjee, P., Raftery, M., . . . Sachdev, P. S. (2016). Changes in the plasma proteome at asymptomatic and symptomatic stages of autosomal dominant Alzheimer’s disease. Scientific Reports, 6, 29078.
https://doi.org/10.1038/srep29078