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Brain Cells Derived from Alzheimer's Disease Patients have Multiple Specific Innate Abnormalities in Energy Metabolismopen access

Authors
Ryu, Woo-InBormann, Mariana K.Shen, MinqiKim, DohoonForester, BrentPark, YeongwonSo, JisunSeo, HyemyungSonntag, Kai-C.Cohen, Bruce M.
Issue Date
Oct-2021
Publisher
Nature Publishing Group
Citation
Molecular Psychiatry, v.26, no.10, pp 5702 - 5714
Pages
13
Indexed
SCIE
SCOPUS
Journal Title
Molecular Psychiatry
Volume
26
Number
10
Start Page
5702
End Page
5714
URI
https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/113883
DOI
10.1038/s41380-021-01068-3
ISSN
1359-4184
1476-5578
Abstract
Altered energy metabolism has been implicated both in aging and the pathogenesis of late-onset Alzheimer’s disease (LOAD). However, it is unclear which anomalies are acquired phenotypes and which are inherent and predispose to disease. We report that neural progenitor cells and astrocytes differentiated from LOAD patient-derived induced pluripotent stem cells exhibit multiple inter-related bioenergetic alterations including: changes in energy production by mitochondrial respiration versus glycolysis, as a consequence of alterations in bioenergetic substrate processing and transfer of reducing agents, reduced levels of NAD/NADH, diminished glucose uptake and response rates to insulin (INS)/IGF-1 signaling, decreased INS receptor and glucose transporter 1 densities, and changes in the metabolic transcriptome. Our data confirm that LOAD is a “multi-hit” disorder and provide evidence for innate inefficient cellular energy management in LOAD that likely predisposes to neurodegenerative disease with age. These processes may guide the development and testing of diagnostic procedures or therapeutic agents. © 2021, The Author(s).
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