Age-Dependent Decrease of Mitochondrial Complex II Activity in a Familial Mouse Model for Alzheimer’s Disease

Alzheimer’s disease (AD) is a severe neurodegenerative disorder for which the exact etiology is largely unknown. An increasingly recognized and investigated notion is the pathogenic role of mitochondrial dysfunction in AD. We assessed mitochondrial oxidative-phosphorylation (OXPHOS) enzyme activities in the APPswe/PS1ΔE9 mouse model from 4.5 to 14 months of age. We show an age-dependent decrease in mitochondrial complex-II activity starting at 9 months in APP/PS1 mice. Other enzymes of the OXPHOS do not show any alterations. Since amyloid-β (Aβ) plaques are already present from 4 months of age, mitochondrial dysfunction likely occurs downstream of Aβ pathology in this mouse model.

• Publication year

  2018

• Venue

  Journal of Alzheimer's Disease

• Publication date

  2018-09-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3233/JAD-180337PMID 30248054
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Differential effect of amyloid beta peptides on mitochondrial axonal trafficking depends on their state of aggregation and binding to the plasma membrane

  2018cited by this paper
• Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease

  2017cited by this paper
• Mitochondrial Complex II: At the Crossroads.

  2017cited by this paper
• Mitochondrial genes are altered in blood early in Alzheimer's disease.

  2017cited by this paper
• Inhibition of mitochondrial fragmentation protects against Alzheimer’s disease in rodent model

  2017cited by this paper
• Relationship Between β-Amyloid and Mitochondrial Dynamics

  2017cited by this paper
• Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

  2017cited by this paper
• Mitochondrial dysfunction in the APP/PSEN1 mouse model of Alzheimer's disease and a novel protective role for ascorbate.

  2017cited by this paper
• Alzheimer’s Disease as the Product of a Progressive Energy Deficiency Syndrome in the Central Nervous System: The Neuroenergetic Hypothesis

  2017cited by this paper
• Mitochondrial dynamics changes with age in an APPsw/PS1dE9 mouse model of Alzheimer’s disease

  2017cited by this paper
• Chronic Stress Aggravates Cognitive Impairment and Suppresses Insulin Associated Signaling Pathway in APP/PS1 Mice

  2016cited by this paper
• Mitochondrial dysfunction in a transgenic mouse model expressing human amyloid precursor protein (APP) with the Arctic mutation

  2016cited by this paper
• Mitochondrial Respiration in the Platelets of Patients with Alzheimer's Disease.

  2016cited by this paper
• Alterations in Cerebral Cortical Glucose and Glutamine Metabolism Precedes Amyloid Plaques in the APPswe/PSEN1dE9 Mouse Model of Alzheimer’s Disease

  2016cited by this paper
• Hydroxytyrosol mildly improve cognitive function independent of APP processing in APP/PS1 mice.

  2016influential reference
• Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis.

  2016cited by this paper
• Impaired mitochondrial energy metabolism in Alzheimer's disease: Impact on pathogenesis via disturbed epigenetic regulation of chromatin landscape.

  2015cited by this paper
• Characterization of ATP Alternations in an Alzheimer's Disease Transgenic Mouse Model

  2015cited by this paper
• Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult.

  2014cited by this paper
• Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma.

  2014cited by this paper
• Unsuspected task for an old team: succinate, fumarate and other Krebs cycle acids in metabolic remodeling.

  2014cited by this paper
• Early alterations in energy metabolism in the hippocampus of APPswe/PS1dE9 mouse model of Alzheimer's disease.

  2014cited by this paper
• Comprehensive behavioral characterization of an APP/PS-1 double knock-in mouse model of Alzheimer's disease

  2013cited by this paper
• Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model

  2013cited by this paper
• The Kunitz-protease inhibitor domain in amyloid precursor protein reduces cellular mitochondrial enzymes expression and function.

  2013cited by this paper
• The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy

  2013cited by this paper
• Role of mitochondrial homeostasis and dynamics in Alzheimer's disease.

  2013cited by this paper
• Mitochondria and Cell Bioenergetics: Increasingly Recognized Components and a Possible Etiologic Cause of Alzheimer's Disease

  2012cited by this paper
• Mitochondrial Dysfunction and Immune Activation are Detectable in Early Alzheimer's Disease Blood

  2012cited by this paper
• Mitochondrion-Derived Reactive Oxygen Species Lead to Enhanced Amyloid Beta Formation

  2012cited by this paper
• Abnormal Mitochondrial Dynamics in the Pathogenesis of Alzheimer's Disease

  2012cited by this paper
• Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain.

  2011cited by this paper
• Biochemical diagnosis of mitochondrial disorders

  2010cited by this paper
• Decreased Numeric Density of Succinic Dehydrogenase-Positive Mitochondria in CA1 Pyramidal Neurons of 3xTg-AD Mice

  2010cited by this paper
• A free radical‐generating system regulates APP metabolism/processing

  2010cited by this paper
• Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model

  2010cited by this paper
• Episodic memory deficits are not related to altered glutamatergic synaptic transmission and plasticity in the CA1 hippocampus of the APPswe/PS1δE9-deleted transgenic mice model of ß-amyloidosis.

  2010cited by this paper
• Succinate dehydrogenase - Assembly, regulation and role in human disease.

  2010cited by this paper
• Reassessing the amyloid cascade hypothesis of Alzheimer's disease.

  2009cited by this paper
• DHA and cholesterol containing diets influence Alzheimer-like pathology, cognition and cerebral vasculature in APPswe/PS1dE9 mice.

  2009cited by this paper
• Amyloid- (cid:1) and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice

  2009cited by this paper
• Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice.

  2009cited by this paper
• Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease

  2009cited by this paper
• Age‐related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild‐type mice

  2008cited by this paper
• Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons

  2008cited by this paper
• Mice with mitochondrial complex I deficiency develop a fatal encephalomyopathy.

  2008cited by this paper
• Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression.

  2008cited by this paper
• Amyloid-β-Induced Mitochondrial Dysfunction

  2007cited by this paper
• Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts.

  2007cited by this paper
• Succinate inhibition of α-ketoglutarate-dependent enzymes in a yeast model of paraganglioma

  2007cited by this paper
• Amyloid-beta-induced mitochondrial dysfunction.

  2007cited by this paper
• Succinate inhibition of alpha-ketoglutarate-dependent enzymes in a yeast model of paraganglioma.

  2007cited by this paper
• Measurement of the energy-generating capacity of human muscle mitochondria: diagnostic procedure and application to human pathology.

  2006cited by this paper
• Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease.

  2006cited by this paper
• Impaired platelet mitochondrial activity in Alzheimer's disease and mild cognitive impairment.

  2006cited by this paper
• Accumulation of Amyloid Precursor Protein in the Mitochondrial Import Channels of Human Alzheimer’s Disease Brain Is Associated with Mitochondrial Dysfunction

  2006cited by this paper
• Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease

  2005cited by this paper
• Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease.

  2005cited by this paper
• Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities.

  2005cited by this paper
• Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase.

  2004cited by this paper
• Pathways towards and away from Alzheimer's disease

  2004cited by this paper
• A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease.

  2004cited by this paper
• Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase

  2004cited by this paper
• Function and structure of complex II of the respiratory chain.

  2003cited by this paper
• Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells

  2003cited by this paper
• Hippocampal Aβ42 Levels Correlate with Spatial Memory Deficit in APP and PS1 Double Transgenic Mice

  2002cited by this paper
• Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease.

  2002cited by this paper
• Functional mitochondria are required for amyloid β‐mediated neurotoxicity

  2001cited by this paper
• Co-expression of multiple transgenes in mouse CNS: a comparison of strategies.

  2001cited by this paper
• Glutathione Depletion, Lipid Peroxidation and Mitochondrial Dysfunction Are Induced by Chronic Stress in Rat Brain

  2001cited by this paper
• β‐Amyloid inhibits integrated mitochondrial respiration 
and key enzyme activities

  2001cited by this paper
• Energy Hypometabolism in Posterior Cingulate Cortex of Alzheimer's Patients: Superficial Laminar Cytochrome Oxidase Associated with Disease Duration

  2001cited by this paper
• Decreased levels of complex III core protein 1 and complex V β chain in brains from patients with Alzheimer’s disease and Down syndrome

  2000cited by this paper
• A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients.

  2000cited by this paper
• Calcium Homeostasis and Reactive Oxygen Species Production in Cells Transformed by Mitochondria from Individuals with Sporadic Alzheimer’s Disease

  1997cited by this paper
• Clinical heterogeneity in respiratory chain complex III deficiency in childhood.

  1997cited by this paper
• Controlling the false discovery rate: a practical and powerful approach to multiple testing

  1995influential reference
• Differential investigation of the capacity of succinate oxidation in human skeletal muscle.

  1985cited by this paper
• The mitochondrial electron transport and oxidative phosphorylation system.

  1985cited by this paper
• [1] Citrate synthase. [EC 4.1.3.7. Citrate oxaloacetate-lyase (CoA-acetylating)]

  1969cited by this paper
• A microspectrophotometric method for the determination of cytochrome oxidase.

  1951cited by this paper

• PEX11β-mediated improvement of mitochondrial dysfunction restores behavioral defect and cellular viability in neuropathological conditions

  2025cites this paper
• Organelle abnormalities in Alzheimer's disease.

  2025cites this paper
• Organelle stresses and energetic metabolisms promote endothelial–to–mesenchymal transition and fibrosis via upregulating FOSB and MEOX1 in Alzheimer’s disease

  2025cites this paper
• Nervonic acid and 15-epi-PGA1 mediate systemic mitochondrial dysfunction in AD dementia.

  2025cites this paper
• Endogenously generated Dutch-type Aβ nonfibrillar aggregates dysregulate presynaptic neurotransmission in the absence of detectable inflammation

  2025cites this paper
• Age- and sex-associated alterations in hypothalamic mitochondrial bioenergetics and inflammatory-associated signaling in the 3xTg mouse model of Alzheimer’s disease

  2024cites this paper
• Mitochondrial Complex I and β-Amyloid Peptide Interplay in Alzheimer’s Disease: A Critical Review of New and Old Little Regarded Findings

  2023cites this paper
• Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases

  2023cites this paper
• Mitochondrial Transfusion Improves Mitochondrial Function Through Up-regulation of Mitochondrial Complex II Protein Subunit SDHB in the Hippocampus of Aged Mice

  2022cites this paper
• Assessment of Mitochondrial Complex II and III Activity in Brain Sections: A Histoenzymological Technique.

  2022cites this paper
• Development of Neuroprotective Agents for the Treatment of Alzheimer's Disease Using Conjugates of Serotonin with Sesquiterpene Lactones.

  2022cites this paper
• Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease

  2021cites this paper
• Effects of Mild Excitotoxic Stimulus on Mitochondria Ca2+ Handling in Hippocampal Cultures of a Mouse Model of Alzheimer’s Disease

  2021cites this paper
• Activation of ERK–Drp1 signaling promotes hypoxia‐induced Aβ accumulation by upregulating mitochondrial fission and BACE1 activity

  2021cites this paper
• Accumulation of amyloid precursor protein C-terminal fragments triggers mitochondrial structure, function, and mitophagy defects in Alzheimer’s disease models and human brains

  2020cites this paper
• Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr−/−.Leiden mice

  2020cites this paper
• Parkin overexpression attenuates Aβ-induced mitochondrial dysfunction in HEK293 cells by restoring impaired mitophagy.

  2020cites this paper
• Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr^{â‹TM/â‹TM}.Leiden mice

  2020cites this paper
• Alzheimer’s disease improved through the activity of mitochondrial chain complexes and their gene expression in rats by boswellic acid

  2020cites this paper
• Oxidative Phosphorylation Impairment by DDT and DDE

  2019cites this paper