BRAIN AEROBIC GLYCOLYSIS AND TAU DEPOSITION WITH [18F]-AV-1451 PET

Abstract

Our previous studies demonstrated that the aerobic glycolysis (AG, non-oxidative part of brain glucose metabolism), a marker of metabolic functions involved in synaptic plasticity and neuroprotection, declines with age on the whole brain level. This decline is greatest in regions known to accumulate a high density of beta-amyloid plaques in Alzheimer's disease (AD). These observations suggest that there is a substantial age-related loss in metabolic brain reserve supporting synaptic plasticity and neuroprotection that may introduce a selective vulnerability to processes leading to AD pathology and cognitive decline. Neurofibrillary tau pathology is a marker of cell death and dysfunction but little is known about the relationship between regional AG and tau pathology in the human brain in vivo. Our previous tau PET imaging studies with AV-1451 demonstrated tau deposition in several brain regions, including enthorhinal, temporal, lateral occipital, and parietal cortex. Here we present our preliminary evaluation of the relationship between AG, metabolism, blood flow and tau deposition. Thirty five individuals (32 cognitively normal, 15 females, 53–88 years old) underwent PET studies using inhalation of 15O-CO and 15O-O2, and injection of 15O-water, 18F-fluorodeoxyglucose, and [18F]-AV-1451. AG, cerebral metabolic rate of glucose (CMRGlu) and oxygen (CMRO2), cerebral blood flow (CBF), and tau deposition were calculated and corrected for partial volume effects in regions of interest defined using FreeSurfer. Association between AG, CMRGlu, CMRO2, CBF and AV-1451 deposition was evaluated using linear regression models, both unadjusted and adjusted for age and gender. A negative correlation was demonstrated between tau deposition and AG in lateral occipital, inferior and superior parietal cortices, suggesting that higher AG levels are associated with less tau deposition. This association remained significant after adjusting for age and gender for lateral occipital (F1,31=8.632, p=0.006) and superior parietal (F1,31=12.367, p=0.001). Tau deposition correlated to CMRGlu in superior parietal cortex (F1,31=4.856; p=0.035). No correlation was demonstrated between tau deposition and CMRO2 and CBF. Our findings support the hypothesis that in regions known to accumulate AD pathology, higher levels of AG are associated with lower pathological burden, suggesting that high AG promotes resilience to progression of AD pathology.