Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons

Winnie S. Liang, Eric M. Reiman, Jon Valla, Travis Dunckley, Thomas G. Beach, Andrew Grover, Tracey L. Niedzielko, Lonnie E. Schneider, Diego Mastroeni, Richard Caselli, Walter Kukull, John C. Morris, Christine M. Hulette, Donald Schmechel, Joseph Rogers, Dietrich A. Stephan

Research output: Contribution to journalArticle

301 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is associated with regional reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose, which may begin long before the onset of histopathological or clinical features, especially in carriers of a common AD susceptibility gene. Molecular evaluation of cells from metabolically affected brain regions could provide new information about the pathogenesis of AD and new targets at which to aim disease-slowing and prevention therapies. Data from a genome-wide transcriptomic study were used to compare the expression of 80 metabolically relevant nuclear genes from laser-capture microdissected non-tangle-bearing neurons from autopsy brains of AD cases and normal controls in posterior cingulate cortex, which is metabolically affected in the earliest stages; other brain regions metabolically affected in PET studies of AD or normal aging; and visual cortex, which is relatively spared. Compared with controls, AD cases had significantly lower expression of 70% of the nuclear genes encoding subunits of the mitochondrial electron transport chain in posterior cingulate cortex, 65% of those in the middle temporal gyrus, 61% of those in hippocampal CA1, 23% of those in entorhinal cortex, 16% of those in visual cortex, and 5% of those in the superior frontal gyrus. Western blots confirmed underexpression of those complex I-V subunits assessed at the protein level. Cerebral metabolic rate for glucose abnormalities in FDG PET studies of AD may be associated with reduced neuronal expression of nuclear genes encoding subunits of the mitochondrial electron transport chain.

Original languageEnglish (US)
Pages (from-to)4441-4446
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number11
DOIs
StatePublished - Mar 18 2008
Externally publishedYes

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Gyrus Cinguli
Energy Metabolism
Alzheimer Disease
Neurons
Genes
Visual Cortex
Electron Transport
Positron-Emission Tomography
Glucose
Entorhinal Cortex
Disease Susceptibility
Brain
Brain Diseases
Temporal Lobe
Prefrontal Cortex
Autopsy
Lasers
Western Blotting
Genome
Gene Expression

Keywords

  • Affymetrix microarrays
  • Gene expression
  • Laser capture micro-dissection

ASJC Scopus subject areas

  • General

Cite this

Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. / Liang, Winnie S.; Reiman, Eric M.; Valla, Jon; Dunckley, Travis; Beach, Thomas G.; Grover, Andrew; Niedzielko, Tracey L.; Schneider, Lonnie E.; Mastroeni, Diego; Caselli, Richard; Kukull, Walter; Morris, John C.; Hulette, Christine M.; Schmechel, Donald; Rogers, Joseph; Stephan, Dietrich A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 11, 18.03.2008, p. 4441-4446.

Research output: Contribution to journalArticle

Liang, WS, Reiman, EM, Valla, J, Dunckley, T, Beach, TG, Grover, A, Niedzielko, TL, Schneider, LE, Mastroeni, D, Caselli, R, Kukull, W, Morris, JC, Hulette, CM, Schmechel, D, Rogers, J & Stephan, DA 2008, 'Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 11, pp. 4441-4446. https://doi.org/10.1073/pnas.0709259105
Liang, Winnie S. ; Reiman, Eric M. ; Valla, Jon ; Dunckley, Travis ; Beach, Thomas G. ; Grover, Andrew ; Niedzielko, Tracey L. ; Schneider, Lonnie E. ; Mastroeni, Diego ; Caselli, Richard ; Kukull, Walter ; Morris, John C. ; Hulette, Christine M. ; Schmechel, Donald ; Rogers, Joseph ; Stephan, Dietrich A. / Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 11. pp. 4441-4446.
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abstract = "Alzheimer's disease (AD) is associated with regional reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose, which may begin long before the onset of histopathological or clinical features, especially in carriers of a common AD susceptibility gene. Molecular evaluation of cells from metabolically affected brain regions could provide new information about the pathogenesis of AD and new targets at which to aim disease-slowing and prevention therapies. Data from a genome-wide transcriptomic study were used to compare the expression of 80 metabolically relevant nuclear genes from laser-capture microdissected non-tangle-bearing neurons from autopsy brains of AD cases and normal controls in posterior cingulate cortex, which is metabolically affected in the earliest stages; other brain regions metabolically affected in PET studies of AD or normal aging; and visual cortex, which is relatively spared. Compared with controls, AD cases had significantly lower expression of 70{\%} of the nuclear genes encoding subunits of the mitochondrial electron transport chain in posterior cingulate cortex, 65{\%} of those in the middle temporal gyrus, 61{\%} of those in hippocampal CA1, 23{\%} of those in entorhinal cortex, 16{\%} of those in visual cortex, and 5{\%} of those in the superior frontal gyrus. Western blots confirmed underexpression of those complex I-V subunits assessed at the protein level. Cerebral metabolic rate for glucose abnormalities in FDG PET studies of AD may be associated with reduced neuronal expression of nuclear genes encoding subunits of the mitochondrial electron transport chain.",
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AU - Beach, Thomas G.

AU - Grover, Andrew

AU - Niedzielko, Tracey L.

AU - Schneider, Lonnie E.

AU - Mastroeni, Diego

AU - Caselli, Richard

AU - Kukull, Walter

AU - Morris, John C.

AU - Hulette, Christine M.

AU - Schmechel, Donald

AU - Rogers, Joseph

AU - Stephan, Dietrich A.

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N2 - Alzheimer's disease (AD) is associated with regional reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose, which may begin long before the onset of histopathological or clinical features, especially in carriers of a common AD susceptibility gene. Molecular evaluation of cells from metabolically affected brain regions could provide new information about the pathogenesis of AD and new targets at which to aim disease-slowing and prevention therapies. Data from a genome-wide transcriptomic study were used to compare the expression of 80 metabolically relevant nuclear genes from laser-capture microdissected non-tangle-bearing neurons from autopsy brains of AD cases and normal controls in posterior cingulate cortex, which is metabolically affected in the earliest stages; other brain regions metabolically affected in PET studies of AD or normal aging; and visual cortex, which is relatively spared. Compared with controls, AD cases had significantly lower expression of 70% of the nuclear genes encoding subunits of the mitochondrial electron transport chain in posterior cingulate cortex, 65% of those in the middle temporal gyrus, 61% of those in hippocampal CA1, 23% of those in entorhinal cortex, 16% of those in visual cortex, and 5% of those in the superior frontal gyrus. Western blots confirmed underexpression of those complex I-V subunits assessed at the protein level. Cerebral metabolic rate for glucose abnormalities in FDG PET studies of AD may be associated with reduced neuronal expression of nuclear genes encoding subunits of the mitochondrial electron transport chain.

AB - Alzheimer's disease (AD) is associated with regional reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose, which may begin long before the onset of histopathological or clinical features, especially in carriers of a common AD susceptibility gene. Molecular evaluation of cells from metabolically affected brain regions could provide new information about the pathogenesis of AD and new targets at which to aim disease-slowing and prevention therapies. Data from a genome-wide transcriptomic study were used to compare the expression of 80 metabolically relevant nuclear genes from laser-capture microdissected non-tangle-bearing neurons from autopsy brains of AD cases and normal controls in posterior cingulate cortex, which is metabolically affected in the earliest stages; other brain regions metabolically affected in PET studies of AD or normal aging; and visual cortex, which is relatively spared. Compared with controls, AD cases had significantly lower expression of 70% of the nuclear genes encoding subunits of the mitochondrial electron transport chain in posterior cingulate cortex, 65% of those in the middle temporal gyrus, 61% of those in hippocampal CA1, 23% of those in entorhinal cortex, 16% of those in visual cortex, and 5% of those in the superior frontal gyrus. Western blots confirmed underexpression of those complex I-V subunits assessed at the protein level. Cerebral metabolic rate for glucose abnormalities in FDG PET studies of AD may be associated with reduced neuronal expression of nuclear genes encoding subunits of the mitochondrial electron transport chain.

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