TY - JOUR
T1 - Aerobic glycolysis and tau deposition in preclinical Alzheimer's disease
AU - Vlassenko, Andrei G.
AU - Gordon, Brian A.
AU - Goyal, Manu S.
AU - Su, Yi
AU - Blazey, Tyler M.
AU - Durbin, Tony J.
AU - Couture, Lars E.
AU - Christensen, Jon J.
AU - Jafri, Hussain
AU - Morris, John C.
AU - Raichle, Marcus E.
AU - Benzinger, Tammie L.S.
N1 - Funding Information:
This work was supported by National Institutes of Health [P50 AG05681, P01 AG026276, P01 AG03991, R01 AG043434, R01 AG053503, R01 AG057536, UL1 TR000448, P30 NS098577, R01 EB009352]; the Dana Foundation, the Hope Center for Neurological Disorders, the Foundation for the American Society of Neuroradiology, Foundation for Barnes-Jewish Hospital, and the Charles and Joanne Knight Alzheimer Disease Initiative. Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) provided the technology transfer for production of AV-1451 and also the precursor.
Funding Information:
A.G.V., B.A.G., M.S.G., Y.S., T.M.B., T.J.D., L.E.C., J.J.C., H.J., and M.E.R. have nothing to report. T.L-.S.B. receives research support from grants from NIH and from Eli Lilly, Avid Radiopharmaceuticals, and Roche, Johnson & Johnson, and Biogen (clinical trials), outside the submitted work. J.C.M. is currently participating in clinical trials of antidementia drugs from Eli Lilly and Company, Biogen, and Janssen. J.C.M. serves as a consultant for Lilly USA. He receives research support from Eli Lilly/Avid Radiopharmaceuticals and is funded by NIH grants # P50AG005681, P01AG003991, P01AG026276, and UF01AG032438.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/7
Y1 - 2018/7
N2 - Research of the human brain metabolism in vivo has largely focused on total glucose use (via fluorodeoxyglucose positron emission tomography) and, until recently, did not examine the use of glucose outside oxidative phosphorylation, which is known as aerobic glycolysis (AG). AG supports important functions including biosynthesis and neuroprotection but decreases dramatically with aging. This multitracer positron emission tomography study evaluated the relationship between AG, total glucose use (CMRGlc), oxygen metabolism (CMRO2), tau, and amyloid deposition in 42 individuals, including those at preclinical and symptomatic stages of Alzheimer's disease. Our findings demonstrate that in individuals with amyloid burden, lower AG is associated with higher tau deposition. No such correlation was observed for CMRGlc or CMRO2. We suggest that aging-related loss of AG leading to decreased synaptic plasticity and neuroprotection may accelerate tauopathy in individuals with amyloid burden. Longitudinal AG and Alzheimer's disease pathology studies are needed to verify causality.
AB - Research of the human brain metabolism in vivo has largely focused on total glucose use (via fluorodeoxyglucose positron emission tomography) and, until recently, did not examine the use of glucose outside oxidative phosphorylation, which is known as aerobic glycolysis (AG). AG supports important functions including biosynthesis and neuroprotection but decreases dramatically with aging. This multitracer positron emission tomography study evaluated the relationship between AG, total glucose use (CMRGlc), oxygen metabolism (CMRO2), tau, and amyloid deposition in 42 individuals, including those at preclinical and symptomatic stages of Alzheimer's disease. Our findings demonstrate that in individuals with amyloid burden, lower AG is associated with higher tau deposition. No such correlation was observed for CMRGlc or CMRO2. We suggest that aging-related loss of AG leading to decreased synaptic plasticity and neuroprotection may accelerate tauopathy in individuals with amyloid burden. Longitudinal AG and Alzheimer's disease pathology studies are needed to verify causality.
KW - Aging
KW - Alzheimer's disease
KW - Amyloid imaging
KW - Brain aerobic glycolysis
KW - Cerebral metabolic rate of glucose
KW - Cerebral metabolic rate of oxygen
KW - Positron emission tomography
KW - Tau imaging
UR - http://www.scopus.com/inward/record.url?scp=85045199726&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2018.03.014
DO - 10.1016/j.neurobiolaging.2018.03.014
M3 - Article
C2 - 29655050
AN - SCOPUS:85045199726
SN - 0197-4580
VL - 67
SP - 95
EP - 98
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -