Aerobic glycolysis and tau deposition in preclinical Alzheimer's disease

Neurobiol Aging. 2018 Jul;67:95-98. doi: 10.1016/j.neurobiolaging.2018.03.014. Epub 2018 Mar 20.

Abstract

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.

Keywords: Aging; Alzheimer's disease; Amyloid imaging; Brain aerobic glycolysis; Cerebral metabolic rate of glucose; Cerebral metabolic rate of oxygen; Positron emission tomography; Tau imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerobiosis
  • Aged
  • Aged, 80 and over
  • Aging / metabolism*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloidogenic Proteins / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / pathology
  • Female
  • Glucose / metabolism
  • Glycolysis*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuronal Plasticity
  • Oxygen Consumption
  • Positron-Emission Tomography
  • tau Proteins / metabolism*

Substances

  • Amyloidogenic Proteins
  • tau Proteins
  • Glucose