P2‐216: LOW GLUCOSE UTILIZATION AND HIGH LACTATE PRODUCTION IN THE ALZHEIMER'S DISEASE BRAIN

Abstract

Background: In Alzheimer's disease (AD), the precuneus shows early Abeta deposition and decreased glucose utilization (Landau et al., 2012). Its vulnerability has been linked to metabolic reliance on glycolysis (Vaishnavi et al., 2010; Vlassenko et al., 2010). We hypothesized that, in AD, the precuneus shows higher concentrations of glucose (reflecting decreased utilization) and lactate (end product of glycolysis). Methods: We studied 22 patients with probable AD and Clinical Dementia Rating (CDR) 0.5 or 1, and 32 control subjects using two-dimensional magnetic resonance Spectroscopy (J-PRESS MRS). Data were acquired from a voxel over bilateral precuneus and analyzed using ProFit to determine metabolite concentrations. We used mixed models to examine whether glucose (Glc) and lactate (Lac) concentrations (relative to creatine, Cr) differed in patients and controls covarying age. To assess the pathophysiological significance of glucose and lactate concentrations, we examined their association with CSFA beta 42 (reflecting brain amyloidosis), and tau and p 181 -tau (reflecting neurodegeneration). Results: Patients compared to controls had significantly higher glucose (F = 6.4; p = 0.015; Fig. a) and lactate (F = 5.1; p = 0.028; Fig. b) concentrations; age was not significantly associated with either metabolite. Glucose was positively correlated with CSF tau (R=0.63; p=0.002; Fig. c) and p 181 -tau (R = 0.48; p = 0.017), but not A beta 42. Lactate was not correlated with any CSF biomarker. The Figure depicts estimated marginal means and standard errors from the mixed model. Conclusions: Patients with early AD have higher glucose concentration in an area susceptible to AD pathology compared to controls, perhaps as a result of lower glucose utilization due to neurogeneration. In addition, lactate concentration is higher, suggesting higher regional metabolic reliance on glycolysis. These results motivate the longitudinal study of MRS glucose and lactate as novel AD biomarkers. (Figure Presented).