Brain aerobic glycolysis and resilience in Alzheimer disease

Abstract

The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aβ) 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.

A new framework for metabolic connectivity mapping using bolus [18F]FDG PET and kinetic modeling

“…Fifty-four healthy adults (mean age 57.4 AE 14.8 years, 24 males) underwent [ 18 F]FDG PET and MRI scans as part of the Adult Metabolism & Brain Resilience (AMBR) study. 25 This study was performed according to the principles outlines in the Declaration of Helsinki. All assessments and imaging procedures were approved by Human Research Protection Office and Radioactive Drug Research Committee at Washington University in St. Louis.…”

Futoquinol improves Aβ25–35‐induced memory impairment in mice by inhibiting the activation of p38MAPK through the glycolysis pathway and regulating the composition of the gut microbiota

“…Wang et al, 2023). There is increasing evidence that the changes in aerobic glycolysis are closely related to AD pathogenesis (Goyal et al, 2023;Jo et al, 2022). In the process of inflammatory activation, cell metabolism is reprogrammed from oxidative phosphorylation to aerobic glycolysis, thus aggravating the occurrence of AD (Baik et al, 2019).…”

“…Impaired glucose metabolism in the brain is an important physiological feature of AD, closely related to its development and cognitive dysfunction (Preziuso et al, 2023; Z. J. Wang et al, 2023). There is increasing evidence that the changes in aerobic glycolysis are closely related to AD pathogenesis (Goyal et al, 2023; Jo et al, 2022). In the process of inflammatory activation, cell metabolism is reprogrammed from oxidative phosphorylation to aerobic glycolysis, thus aggravating the occurrence of AD (Baik et al, 2019).…”

The controllosphere: The neural origin of cognitive effort.

“…This hypothesis attributes cognitive effort to the rate of waste accumulation and cognitive fatigue to the total accumulated waste. Suggestively, amyloid-β proteins are heavily deposited in brain regions characterized by elevated levels of aerobic glycolysis (Vlassenko et al, 2010), which may protect against Alzheimer’s disease (Goyal et al, 2023). However, preliminary evidence for the amyloid-β hypothesis of cognitive effort is mixed (Aschenbrenner et al, 2022; Papadopetraki et al, 2021), and even the putative contribution of amyloid-β to Alzheimer’s disease is now being reconsidered (Piller, 2022).…”