TY - JOUR
T1 - Brain aerobic glycolysis and resilience in Alzheimer disease
AU - Goyal, Manu S.
AU - Blazey, Tyler
AU - Metcalf, Nicholas V.
AU - McAvoy, Mark P.
AU - Strain, Jeremy F.
AU - Rahmani, Maryam
AU - Durbin, Tony J.
AU - Xiong, Chengjie
AU - Benzinger, Tammie L.S.
AU - Morris, John C.
AU - Raichle, Marcus E.
AU - Vlassenko, Andrei G.
N1 - Funding Information:
ACKNOWLEDGMENTS. We greatly appreciate Jennifer Byers and Kim Casey for their ongoing efforts in participant recruitment and acquiring data. We thank Abraham Z. Snyder, Matthew R. Brier, and Lars E. Couture for their advice on the analyses of the PET and MRI imaging data. We also thank other past and present members and students of the Vlassenko-Goyal lab for their assistance in data collection, management, and analysis. We are particularly grateful for our research participants and their families for their altruism. We also acknowledge the directors and staff of the Neuroimaging Labs Research Center,KnightAlzheimer’s Disease Research Center,Center for Clinical Imaging Research (CCIR), and the Washington University cyclotron facility for making this research possible. Finally, we thank our reviewers for their critical and thoughtful questions and comments. Funding for this research was provided by the Barnes-Jewish Hospital Foundation (J.C.M.), the James S. McDonnell
Funding Information:
We greatly appreciate Jennifer Byers and Kim Casey for their ongoing efforts in participant recruitment and acquiring data. We thank Abraham Z. Snyder, Matthew R. Brier, and Lars E. Couture for their advice on the analyses of the PET and MRI imaging data. We also thank other past and present members and students of the Vlassenko-Goyal lab for their assistance in data collection, management, and analysis. We are particularly grateful for our research participants and their families for their altruism. We also acknowledge the directors and staff of the Neuroimaging Labs Research Center, Knight Alzheimer's Disease Research Center, Center for Clinical Imaging Research (CCIR), and the Washington University cyclotron facility for making this research possible. Finally, we thank our reviewers for their critical and thoughtful questions and comments. Funding for this research was provided by the Barnes-Jewish Hospital Foundation (J.C.M.), the James S. McDonnell Foundation, the McDonnell Center for Systems Neuroscience, the NIH/NIA R01AG053503 (A.G.V., M.E.R.), R01AG057536 (A.G.V., M.S.G.), RF1AG073210 (A.G.V., M.S.G.), P50AG0005681 (J.C.M.), P01AG026276 (J.C.M.), and P01AG003991 (J.C.M., T.L.-S.B.). Some of the MRI sequences used in the CCIR to produce the AMBR dataset were obtained from the Massachusetts General Hospital. Support for Florbetapir-F18 scans at the Knight ADRC was provided by Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly.
Publisher Copyright:
Copyright © 2023 the Author(s).
PY - 2023/2/14
Y1 - 2023/2/14
N2 - The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aâ) deposition in individuals with symptomatic and preclinical Alzheimer disease (AD). Brain AG decreases with age, but the functional significance of this decrease with regard to the development of AD symptomatology is poorly understood. Using PET measurements of regional blood flow, oxygen consumption, and glucose utilization-from which we derive AG-we find that cognitive impairment is strongly associated with loss of the typical youthful pattern of AG. In contrast, amyloid positivity without cognitive impairment was associated with preservation of youthful brain AG, which was even higher than that seen in cognitively unimpaired, amyloid negative adults. Similar findings were not seen for blood flow nor oxygen consumption. Finally, in cognitively unimpaired adults, white matter hyperintensity burden was found to be specifically associated with decreased youthful brain AG. Our results suggest that AG may have a role in the resilience and/or response to early stages of amyloid pathology and that age-related white matter disease may impair this process.
AB - The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aâ) deposition in individuals with symptomatic and preclinical Alzheimer disease (AD). Brain AG decreases with age, but the functional significance of this decrease with regard to the development of AD symptomatology is poorly understood. Using PET measurements of regional blood flow, oxygen consumption, and glucose utilization-from which we derive AG-we find that cognitive impairment is strongly associated with loss of the typical youthful pattern of AG. In contrast, amyloid positivity without cognitive impairment was associated with preservation of youthful brain AG, which was even higher than that seen in cognitively unimpaired, amyloid negative adults. Similar findings were not seen for blood flow nor oxygen consumption. Finally, in cognitively unimpaired adults, white matter hyperintensity burden was found to be specifically associated with decreased youthful brain AG. Our results suggest that AG may have a role in the resilience and/or response to early stages of amyloid pathology and that age-related white matter disease may impair this process.
KW - Alzheimer's disease
KW - aerobic glycolysis
KW - aging
KW - resilience
KW - white matter hyperintensities
UR - http://www.scopus.com/inward/record.url?scp=85147460713&partnerID=8YFLogxK
U2 - 10.1073/pnas.2212256120
DO - 10.1073/pnas.2212256120
M3 - Article
C2 - 36745794
AN - SCOPUS:85147460713
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
M1 - e2212256120
ER -