Aerobic glycolysis and tau deposition in preclinical Alzheimer's disease
Open accessAbstract
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 (CMRO 2), 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 CMRO 2. 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.
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In brains of people with Down syndrome and Down syndrome with Alzheimer disease neuropathology, HNE and protein carbonyl levels are elevated, with greater increases in those with Alzheimer disease.
“Other biomarkers of increased oxidative damage in the brains of persons with DS and persons with DS with AD neuropathology (DS with AD) include elevated levels of HNE and PC15,42; the increases are greater in people with DS with AD62,65,66.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [66]
The Participants and Results sections describe PET measures of aerobic glycolysis, amyloid, and tau in adults with preclinical or mild Alzheimer disease. Our copy does not address Down syndrome or report HNE or protein carbonyl levels; searches for those markers and Down syndrome found no relevant passage. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe oxidatively modified proteins in Down syndrome include proteins linked to altered glucose metabolism, mTOR signaling with inhibited autophagy and increased insulin resistance, and the proteostasis network.
“These oxidatively modified, and likely dysfunctional, proteins include ones associated with altered glucose metabolism, mTOR signaling (including inhibited autophagy and increased insulin resistance), and the proteostasis network42,61,62,65,66.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [66]
The Introduction discusses brain glucose metabolism, and the Discussion links lower aerobic glycolysis with greater tau deposition in people with preclinical or very mild Alzheimer disease; neither passage addresses oxidatively modified proteins in Down syndrome. Searches for Down syndrome, oxidatively modified proteins, mTOR, autophagy, insulin resistance, and proteostasis found no passage supporting the attributed claim. (LLM, conf=0.78)
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Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease
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- Authors
- Vlassenko, A. G., Gordon, B. A., Goyal, M. S., Su, Y., Blazey, T. M., Durbin, T. J., Couture, L. E., Christensen, J. J., Jafri, H., Morris, J. C., Raichle, M. E., & Benzinger, T. L.-S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Vlassenko, Andrei G.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 67
- Pages
- 95-98
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC5955846
- OpenAlex
- W2789361216
- Cited by
- 107
- References
- 21
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 12 · 2023: 12 · 2022: 12 · 2021: 13 · 2020: 15 · 2019: 13 · 2018: 4
- FWCI
- 7.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neurobiology of Aging (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- American Society of Neuroradiology
- National Institutes of Health (UL1TR000448, UL1TR002345)
- National Institute on Aging (R01AG053503, R01AG043434, R01AG054567, R01AG057536, P50AG005681, P01AG003991, U19AG032438, U01AG032438, P01AG026276)
- National Institute of Neurological Disorders and Stroke (P30NS098577)
- National Institute of Biomedical Imaging and Bioengineering (R01EB009352)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- aerobic glycolysis, tau deposition, preclinical Alzheimer's disease, amyloid deposition, brain glucose metabolism, oxygen metabolism, aging, neuroprotection, synaptic plasticity, tauopathy
- MeSH terms
- Aerobiosis, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Female, Glucose, Glycolysis, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuronal Plasticity, Oxygen Consumption, tau Proteins, Positron-Emission Tomography, Amyloidogenic Proteins
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