Reduced Glucose Transporter at the Blood‐Brain Barrier and in Cerebral Cortex in Alzheimer Disease

Abstract

We studied the hexose transporter protein of the frontal and temporal neocortex, hippocampus, putamen, cerebellum, and cerebral microvessels (which constitute the blood-brain barrier) in Alzheimer disease and control subjects by reversible and covalent binding with [3H]cytochalasin B and by immunological reactivity. In Alzheimer disease subjects, we found a marked decrease in the hexose transporter in brain microvessels and in the cerebral neocortex and hippocampus, regions that are most affected in Alzheimer disease, but there were no abnormalities in the putamen or cerebellum. Hexose transporter reduction in cerebral microvessels of Alzheimer subjects is relatively specific because other enzyme markers of brain endothelium were not significantly altered. The low density of the hexose transporter at the blood-brain barrier and in the cerebral cortex in Alzheimer disease may be related to decreased in vivo measurements of cerebral oxidative metabolism.

Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

“…The reported decrease in glucose uptake mediated by stress or by high levels of GCs could place neurons in an energy-compromised environment, which could detrimentally affect neuronal responsiveness to pathophysiological events. In fact, glucose transport impairment precedes ATP depletion in brain, increasing neuronal vulnerability to excitotoxicity by compromising function of ion-motive ATPases (Mark et al, 1995), as it has been seen to occur in some neurodegenerative processes such Ab-induced toxicity, schizophrenia and others (Novelli et al, 1988;Kalaria and Harik, 1989;Sims, 1990;Mark et al, 1997;McDermott and De Silva, 2005) in which the reduction in glucose uptake occurs as an early step in the disease process prior to neuronal degeneration (Pettegrew et al, 1994;Reiman et al, 1996). On the other hand, GCs promote reduction in ATP levels (Tombaugh and Sapolsky, 1992;Lawrence and Sapolsky, 1994).…”

The facilitative glucose transporter GLUT3: 20 years of distinction

“…Marked declines in cerebral glucose metabolism are associated with Alzheimer's disease, especially in the parietal and temporal cortices (28,29,37,54). Initial studies by Kalaria and Harik (59) demonstrated a reduction in the 55-kDa form of GLUT1 in cerebral microvessels prepared from Alzheimer's patients compared with normal age-matched controls (60). These observations were confirmed and extended in studies by Simpson et al, who also demonstrated a loss of the 45-kDa glial form of GLUT1 and a striking loss of GLUT3 protein expression in parietal, occipital, and temporal cortex, together with caudate nucleus and hippocampus; only the frontal cortex did not show any significant loss (109).…”

Immortalized Human Brain Endothelial Cells and Flow-Based Vascular Modeling: A Marriage of Convenience for Rational Neurovascular Studies

“…Loss of BBB structural integrity and function plays a pivotal role in the pathogenesis of many diseases of the central nervous system (CNS). The BBB is altered in many clinical settings including brain trauma (Unterberg et al, 2004), focal brain ischemia (Latour et al, 2004), meningitis (van der et al, 2004), brain tumor (Lee et al, 2006), stroke (Cipolla et al, 2004), inflammation (Stamatovic et al, 2006), Alzheimer's disease (Kalaria, 1992), and multiple sclerosis (Minagar and Alexander, 2003). In ischemic brain injury, matrix metalloproteinases (MMPs) contribute to the disruption of the BBB leading to vasogenic edema, and to the influx of leukocytes into the CNS (Gasche et al, 2006).…”