scholarly journals Glucose transporters in Alzheimer's disease

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S265-S266
Author(s):  
Natalia Kyrtata ◽  
Ben Dickie ◽  
Hedley Emsley ◽  
Laura Parkes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Metabolism ◽  
Animal Models ◽  
Glucose Transport ◽  
Glucose Transporters ◽  
Human Studies ◽  
Glucose Regulation ◽  
Randomised Control Trial ◽  
The Brain

BackgroundPhysiological brain function depends on tight glucose regulation, including transport and phosphorylation, the first step in its metabolism. Impaired glucose regulation is increasingly implicated in the pathophysiology of Alzheimer's disease (AD). Glucose hypometabolism in AD may be at least partly due to impaired glucose transport at the blood-brain barrier (BBB). Glucose transporters (GLUTs) are an integral component of the BBB. There is evidence of a significant reduction in vascular and non-vascular forms of GLUT1 and GLUT3 in AD brains compared to age-matched controls. Glucose transport, as well as phosphorylation, appears to be a rate limiting step for glucose metabolism in the brain. We have reviewed the literature on glucose transport abnormalities in AD and the effect such abnormalities have on the brain.MethodPublished literature between 1st January 1946 and 1st November 2019 was identified using EMBASE and MEDLINE databases and titles and abstracts were scanned. Human studies (autopsy and imaging) and data from animal models were included while reviews, letters and cellular or molecular studies were excluded from the search.ResultAutopsy studies in AD patients show significant reductions in GLUT3 in areas of the brain closely associated with AD pathology. Patients with AD and diabetes showed greater reductions of GLUT1 and GLUT3. A longitudinal study showed significant reductions in GLUT3 levels which correlated with greater amyloid-β (Aβ) and neurofibrillary tangle pathological burden in participants with AD pathology at post-mortem but without evidence of cognitive dysfunction in their lifetime. Some studies showed increased GLUT1, with others showing reduced GLUT1, levels in AD brain. A newly recognised GLUT12 appears to be increased in AD. Animal studies showed similar results with GLUT1 and GLUT3 knockout animal models exhibiting AD pathology, while overexpression of GLUT1 or treatment with metformin decreased Aβ toxicity in a Drosophila model of AD. GLUT2 levels were increased in both human AD brain and in an animal model of AD. Imaging studies using fluorodeoxyglucose [18F]FDG with positron emission tomography (FDG-PET) in AD subjects show reductions in glucose transport and glucose metabolism in areas most affected in AD. A small randomised control trial showed anti-diabetic medications improved the glucose transport in AD subjects.ConclusionGLUTs play a significant role in AD pathology with evidence suggesting that GLUT3 reductions may precede the onset of clinical symptoms, while GLUT2 and GLUT12 may have a compensatory role. Repurposing anti-diabetic drugs shows promising results in both animal and human studies of AD.

scholarly journals A Systematic Review of Glucose Transport Alterations in Alzheimer's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Natalia Kyrtata ◽  
Hedley C. A. Emsley ◽  
Oli Sparasci ◽  
Laura M. Parkes ◽  
Ben R. Dickie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Transport ◽  
Clinical Symptoms ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Glucose Transporters ◽  
Rodent Models ◽  
The Brain

Introduction: Alzheimer's disease (AD) is characterized by cerebral glucose hypometabolism. Hypometabolism may be partly due to reduced glucose transport at the blood-brain barrier (BBB) and across astrocytic and neuronal cell membranes. Glucose transporters (GLUTs) are integral membrane proteins responsible for moving glucose from the bloodstream to parenchymal cells where it is metabolized, and evidence indicates vascular and non-vascular GLUTs are altered in AD brains, a process which could starve the brain of glucose and accelerate cognitive decline. Here we review the literature on glucose transport alterations in AD from human and rodent studies.Methods: Literature published between 1st January 1946 and 1st November 2020 within EMBASE and MEDLINE databases was searched for the terms “glucose transporters” AND “Alzheimer's disease”. Human and rodent studies were included while reviews, letters, and in-vitro studies were excluded.Results: Forty-three studies fitting the inclusion criteria were identified, covering human (23 studies) and rodent (20 studies). Post-mortem studies showed consistent reductions in GLUT1 and GLUT3 in the hippocampus and cortex of AD brains, areas of the brain closely associated with AD pathology. Tracer studies in rodent models of AD and human AD also exhibit reduced uptake of glucose and glucose-analogs into the brain, supporting these findings. Longitudinal rodent studies clearly indicate that changes in GLUT1 and GLUT3 only occur after amyloid-β pathology is present, and several studies indicate amyloid-β itself may be responsible for GLUT changes. Furthermore, evidence from human and rodent studies suggest GLUT depletion has severe effects on brain function. A small number of studies show GLUT2 and GLUT12 are increased in AD. Anti-diabetic medications improved glucose transport capacity in AD subjects.Conclusions: GLUT1 and GLUT3 are reduced in hippocampal and cortical regions in patients and rodent models of AD, and may be caused by high levels of amyloid-β in these regions. GLUT3 reductions appear to precede the onset of clinical symptoms. GLUT2 and GLUT12 appear to increase and may have a compensatory role. Repurposing anti-diabetic drugs to modify glucose transport shows promising results in human studies of AD.

scholarly journals Ceramide and Related-Sphingolipid Levels Are Not Altered in Disease-Associated Brain Regions of APPSLand APPSL/PS1M146LMouse Models of Alzheimer's Disease: Relationship with the Lack of Neurodegeneration?

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Laurence Barrier ◽  
Bernard Fauconneau ◽  
Anastasia Noël ◽  
Sabrina Ingrand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neuronal Death ◽  
Time Course ◽  
Neuronal Loss ◽  
Brain Regions ◽  
App Processing ◽  
Ceramide Accumulation ◽  
The Brain

There is evidence linking sphingolipid abnormalities, APP processing, and neuronal death in Alzheimer's disease (AD). We previously reported a strong elevation of ceramide levels in the brain of the APPSL/PS1Ki mouse model of AD, preceding the neuronal death. To extend these findings, we analyzed ceramide and related-sphingolipid contents in brain from two other mouse models (i.e., APPSLand APPSL/PS1M146L) in which the time-course of pathology is closer to that seen in most currently available models. Conversely to our previous work, ceramides did not accumulate in disease-associated brain regions (cortex and hippocampus) from both models. However, the APPSL/PS1Ki model is unique for its drastic neuronal loss coinciding with strong accumulation of neurotoxic Aβisoforms, not observed in other animal models of AD. Since there are neither neuronal loss nor toxic Aβspecies accumulation in APPSLmice, we hypothesized that it might explain the lack of ceramide accumulation, at least in this model.

scholarly journals Dynamic changes of autophagic flux induced by Abeta in the brain of postmortem Alzheimer’s disease patients, animal models and cell models

Aging ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 10912-10930
Author(s):  
Zhimin Long ◽  
Jingfei Chen ◽  
Yueyang Zhao ◽  
Wen Zhou ◽  
Qiuhui Yao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Autophagic Flux ◽  
Cell Models ◽  
Dynamic Changes ◽  
The Brain

Relationships between amyloid levels, glucose metabolism, morphologic changes in the brain and clinical status of patients with Alzheimer’s disease

2020 ◽  
Vol 34 (5) ◽  
pp. 337-348
Author(s):  
Tanyaluck Thientunyakit ◽  
Chakmeedaj Sethanandha ◽  
Weerasak Muangpaisan ◽  
Orasa Chawalparit ◽  
Kuntarat Arunrungvichian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Metabolism ◽  
Clinical Status ◽  
The Brain ◽  
Morphologic Changes

scholarly journals Ocular Manifestations of Alzheimer’s Disease in Animal Models

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Miles Parnell ◽  
Li Guo ◽  
Mohamed Abdi ◽  
M. Francesca Cordeiro
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Senile Plaques ◽  
Transgenic Animal ◽  
Cellular Level ◽  
Ocular Manifestations ◽  
Transgenic Animal Models ◽  
New Treatments ◽  
The Brain

Alzheimer’s disease (AD) is the most common form of dementia, and the pathological changes of senile plaques (SPs) and neurofibrillary tangles (NFTs) in AD brains are well described. Clinically, a diagnosis remains a postmortem one, hampering both accurate and early diagnosis as well as research into potential new treatments. Visual deficits have long been noted in AD patients, and it is becoming increasingly apparent that histopathological changes already noted in the brain also occur in an extension of the brain; the retina. Due to the optically transparent nature of the eye, it is possible to image the retina at a cellular level noninvasively and thus potentially allow an earlier diagnosis as well as a way of monitoring progression and treatment effects. Transgenic animal models expressing amyloid precursor protein (APP) presenilin (PS) and tau mutations have been used successfully to recapitulate the pathological findings of AD in the brain. This paper will cover the ocular abnormalities that have been detected in these transgenic AD animal models.

Alzheimer's disease biomarkers: Correspondence between human studies and animal models

2013 ◽  
Vol 56 ◽  
pp. 116-130 ◽  
Author(s):  
Jonathan J. Sabbagh ◽  
Jefferson W. Kinney ◽  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Human Studies ◽  
Disease Biomarkers
Sign in / Sign up

Export Citation Format

Share Document