Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ ) deposition

Abstract

Amyloid-β (Aβ) plaque deposition can precede the clinical manifestations of dementia of the Alzheimer type (DAT) by many years and can be associated with changes in brain metabolism. Both the Aβ plaque deposition and the changes in metabolism appear to be concentrated in the brain's default-mode network. In contrast to prior studies of brain metabolism which viewed brain metabolism from a unitary perspective that equated glucose utilization with oxygen consumption, we here report on regional glucose use apart from that entering oxidative phosphorylation (so-called "aerobic glycolysis"). Using PET, we found that the spatial distribution of aerobic glycolysis in normal young adults correlates spatially with Aβ deposition in individuals with DAT and cognitively normal participants with elevated Aβ, suggesting a possible link between regional aerobic glycolysis in young adulthood and later development of Alzheimer pathology.

Fig. 1.

Measurements of ¹¹C-PIB BP (displayed on the y axis) were performed in 11 individuals with DAT (A) and in 14 cognitively normal community-dwelling individuals (B) and, in both cases, were compared with the level of aerobic glycolysis measured in 33 neurological control individuals (x axis). The level of aerobic glycolysis (GI) represents the amount of glucose consumption above or below that predicted by the amount of oxygen. (Further details are given in the text and in ref. .) These data were obtained from 167 nonoverlapping isotropic cubes covering the whole brain that were normalized to the ¹¹C-PIB binding potential cerebellum. (C) The difference between ¹¹C-PIB values in DAT and cognitively normal groups was calculated and plotted against the GI. The strong positive correlation indicates that, although the regional pattern of Aβ distribution remains similar, the slopes of the relationships depicted in A and B differ significantly (P < 10⁻⁴).

Fig. 2.

Maps showing lateral and medial cortical surfaces of the human brain on which are depicted the mean distribution of aerobic glycolysis in units of the GI in 33 neurologically normal young adults and ¹¹C-PIB BP in 11 individuals with DAT. The GI corresponds to the amount of glucose consumption above or below that predicted by the amount of oxygen consumed. (Further details are given in the text and in Fig. 1.)