GLUT-1 Expression in the Cerebra of Patients with Alzheimer’s Disease

doi:10.1016/S0197-4580(97)00111-5

Neurobiology of Aging

Volume 18, Issue 5, September–October 1997, Pages 469-474

https://doi.org/10.1016/S0197-4580(97)00111-5 Get rights and content

Abstract

To investigate the molecular basis of reduced GLUT-1 concentration of the blood–brain barrier in patients with Alzheimer’s disease (AD), the GLUT-1 mass, mRNA content, and structure were studied in eight patients with AD and seven age-matched controls. The results indicate that the 55-kDa GLUT-1 is significantly reduced in AD without a significant change in GLUT-1 mRNA concentrations. Because in some animal models changes in GLUT-1 expression is associated with changes in GLUT-1 mRNA structure, the length of the poly(A) tail of the GLUT-1 mRNA was estimated with a reverse transcription-polymerase chain reaction technique. The length of poly(A) tail of GLUT-1 mRNA in AD subjects was not significantly different from the controls. It is concluded that the AD-related change in GLUT-1 expression is not the result of altered poly(A) length of GLUT-1 mRNA.

Section snippets

Human Subjects

Cerebral tissue samples were obtained from 8 patients (5 women and 3 men; mean age 82 ± 4.6 years) with AD and 7 controls (4 women and 3 men; mean age 79 ± 3.7 years). The tissue samples were made available from St. Louis University Brain Bank. In addition to the clinical history, the diagnosis of AD was pathologically confirmed according to published guidelines 11, 18. The control subjects had no clinical or histological evidence of brain disease. The interval between death and brain sampling

GLUT-1 Protein Content

A representative Western blot of total cerebral proteins and cerebral microvessel proteins is shown in Fig. 3AFig. 3B, respectively. Lanes 1–3 in panel A and Lanes 1,2 in panel B are from control subjects; Lanes 4–6 in panel A and Lanes 3,4 in panel B are from patients with AD. The figure is shown to illustrate the differences in the distribution of various molecular mass forms of GLUT-1 in cerebral microvessels in comparison to total cerebral homogenates. Two discrete bands at 55 kDa and 45

Discussion

The results clearly indicate that the 55-kDa isoform of GLUT-1 is reduced in patients with AD. This is in agreement with a previously published study [30]. However, in the current study the 45-kDa GLUT-1 band was not significantly reduced and we could not reliably identify a 38-kDa band as shown previously [30]. The decrease in 55 kDa GLUT-1 could be demonstrated in both total cerebral homogenates and in isolated cerebral microvessels.

The molecular basis of reduced GLUT-1 concentrations in the

References (33)

P. Bernstein et al.
Poly (A); poly (A) binding proteins and the regulation of mRNA stability
Trends Biochem. Sci.
(1989)
D.R. Gallie et al.
Poly (A) binds to initiation factors and increases cap-dependent translation in vitro
J. Biol. Chem.
(1994)
H.M. Goodman et al.
Cloning of hormone genes from a mixture of cDNA molecules
Methods Enzymol.
(1979)
A.D. Mooradian et al.
Brain uptake of glucose in diabetes mellitusThe role of glucose transporters
Am. J. Med. Sci.
(1991)
A.D. Mooradian et al.
Glucose transport is reduced in the blood brain barrier of aged rats
Brain Res.
(1991)
A.D. Mooradian et al.
β-adrenergic receptor activity of cerebral microvessels in experimental diabetes mellitus
Brain Res.
(1992)
M. Orlowski et al.
Isolation of gamma glutamyl transpeptidase from hog kidney
J. Biol. Chem.
(1965)
E.T. Rosenthal et al.
Sequence-specific adenylations and deadenylations accompany changes in the translation of maternal messenger RNA after fertilization of Spisula oocytes
J. Mol. Biol.
(1983)
E.T. Rosenthal et al.
Widespread changes in the translation and adenylation of maternal messenger RNAs following fertilization of Spisula oocytes
Dev. Biol.
(1987)
G.N. Shah et al.
Age-related shortening of poly (A) tail of albumin mRNA
Arch. Biochem. Biophys.
(1995)

G.N. Shah et al.

Shortening of poly (A) tail of glucose transporter-one mRNA in experimental diabetes mellitus

Brain Res.

(1997)

D.F. Benson et al.

The fluorodeoxyglucose 18F scan in Alzheimer’s disease and multiinfarct dementia

Arch. Neurol.

(1983)

M.J. Bernbaum et al.

Cloning and characterization of a cDNA encoding the rat brain glucose transporter protein

Proc. Natl. Acad. Sci. USA

(1986)

R. Duara et al.

Positron emission tomography in Alzheimer’s disease

Neurology

(1986)

R.P. Friedland et al.

Regional cerebral glucose transport and utilization in Alzheimer’s disease

Neurology

(1989)

D.R. Gallie

The cap and poly (A) tail function synergistically to regulate mRNA translational efficiency

Genes Dev.

(1991)

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Original ArticlesGLUT-1 Expression in the Cerebra of Patients with Alzheimer’s Disease

Abstract

Section snippets

Human Subjects

GLUT-1 Protein Content

Discussion

Trends Biochem. Sci.

J. Biol. Chem.

Methods Enzymol.

Am. J. Med. Sci.

Brain Res.

Brain Res.

J. Biol. Chem.

J. Mol. Biol.

Dev. Biol.

Arch. Biochem. Biophys.

Brain Res.

The fluorodeoxyglucose 18F scan in Alzheimer’s disease and multiinfarct dementia

Arch. Neurol.

Cloning and characterization of a cDNA encoding the rat brain glucose transporter protein

Proc. Natl. Acad. Sci. USA

Positron emission tomography in Alzheimer’s disease

Neurology

Regional cerebral glucose transport and utilization in Alzheimer’s disease

Neurology

The cap and poly (A) tail function synergistically to regulate mRNA translational efficiency

Genes Dev.

Original Articles
GLUT-1 Expression in the Cerebra of Patients with Alzheimer’s Disease