TY - JOUR
T1 - Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis
AU - Haytural, Hazal
AU - Benfeitas, Rui
AU - Schedin-Weiss, Sophia
AU - Bereczki, Erika
AU - Rezeli, Melinda
AU - Unwin, Richard D.
AU - Wang, Xusheng
AU - Dammer, Eric B.
AU - Johnson, Erik C. B.
AU - Seyfried, Nicholas T.
AU - Winblad, Bengt
AU - Tijms, Betty M.
AU - Visser, Pieter Jelle
AU - Frykman, Susanne
AU - Tjernberg, Lars O.
N1 - Funding Information:
The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under Project SNIC 2020/15-164. RDU would like to thank the families and patients who supported this research by donation of brains to the New Zealand Neurological Foundation Human Brain Bank. This project has received funding from Swedish Research Council, Alzheimerfonden, Gun och Bertil Stohnes Stiftelse, Stiftelsen för Gamla Tjänarinnor, Demensfonden, Hjärnfonden, Margaretha af Ugglas’ foundation and Fondation Recherche sur Alzheimer. RDU was supported by Alzheimer’s Research UK (ARUK-PPG2014B-7), Manchester NIHR Biomedical Research Centre and the Greater Manchester Comprehensive Local Research Network and the Stoller Biomarker Discovery Centre which was established with an award from the Medical Research Council (MR/M008959/1). Support for this research was provided by funding from the National Institute on Aging (R01AG053960, R01AG061800, RF1AG057471, RF1AG057470, R01AG057339, RF1AG062181), the Accelerating Medicine Partnership for AD (U01AG046161 and U01AG061357).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.
AB - Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.
UR - https://www.scopus.com/pages/publications/85120913808
U2 - 10.1038/s41597-021-01090-8
DO - 10.1038/s41597-021-01090-8
M3 - Article
C2 - 34862388
SN - 2052-4463
VL - 8
JO - Scientific data
JF - Scientific data
IS - 1
M1 - 312
ER -
SDG 3 Good Health and Well-being