TY - JOUR
T1 - Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies.
AU - Chen,Zhichun,
AU - Zhong,Chunjiu,
Y1 - 2013/07/11/
PY - 2013/04/06/received
PY - 2013/06/03/revised
PY - 2013/06/18/accepted
PY - 2013/7/16/entrez
PY - 2013/7/16/pubmed
PY - 2014/3/22/medline
KW - (11)C-Pittsbergh compound
KW - (18)F-fluorodeoxyglucose
KW - 8-OHG
KW - 8-hydroxyguanosine
KW - AD
KW - AD neuroimaging initiative
KW - ADNI
KW - ADP
KW - AGEs
KW - APOE
KW - APP
KW - APP C-terminal fragments
KW - APP-CTFs
KW - ATP
KW - Advanced glycation endproducts
KW - Alzheimer's disease
KW - Apoptosis
KW - Autophagy
KW - Aβ
KW - BBB
KW - CHEIs
KW - CMRglu
KW - CNS
KW - COX
KW - CSF
KW - Cerebral hypometabolism
KW - Excitotoxicity
KW - FDG
KW - G6PDH
KW - GLP-1
KW - GLUT
KW - GSK-3
KW - Glucagon-like peptide-1
KW - Glycogen synthase kinase 3
KW - IDE
KW - IGF-1
KW - IR
KW - IR substrate-1
KW - IRS-1
KW - Insulin resistance
KW - KGDHC
KW - LTP
KW - MAPK
KW - MCI
KW - MMSE
KW - MR
KW - Mitochondrial dysfunction
KW - N-methyl-D-aspartic acid receptor
KW - NFTs
KW - NMDAR
KW - NSAID
KW - Oxidative stress
KW - PDHC
KW - PET
KW - PI3K
KW - PKM2
KW - PPP
KW - PS1
KW - Peroxisome proliferator-activated receptors
KW - PiB
KW - Positron emission tomography
KW - RAGE
KW - ROS
KW - STZ
KW - T1DM
KW - T2DM
KW - TCA
KW - TD
KW - TDP
KW - TDPase
KW - TGF
KW - TMP
KW - TMPase
KW - TPK
KW - Tau
KW - Thiamine
KW - adenosine driphosphate
KW - adenosine triphosphate
KW - advanced glycation end products
KW - amyloid precursor protein
KW - apolipoprotein E
KW - blood brain barrier
KW - central nervous system
KW - cerebral metabolic rate of glucose
KW - cerebrospinal fluid
KW - cholinesterase inhibitors
KW - cytochrome c oxidase
KW - glucagon-like peptide-1
KW - glucose transporter
KW - glucose-6-phosphate dehydrogenase
KW - glycogen synthase kinase-3
KW - insulin receptor
KW - insulin-degrading enzyme
KW - insulin-like growth factor-1
KW - long term potentiation
KW - mTOR
KW - magnetic resonance
KW - mild cognitive impairment
KW - mitogen-activated protein kinase
KW - neurofibrillary tangles
KW - non-steroidal anti-inflammatory drug
KW - pentose phosphate pathway
KW - phosphatidylinositide 3-kinases
KW - positron emission tomography
KW - presenilin-1
KW - pyruvate dehydrogenase complex
KW - pyruvate kinase isozyme type M2
KW - rCBF
KW - rCMRGlu
KW - reactive oxygen species
KW - regional CMRGlu
KW - regional cerebral blood flow
KW - streptozotocin
KW - the Mini-Mental State Examination
KW - the mammalian target of rapamycin
KW - the receptor of AGEs
KW - thiamine deficiency
KW - thiamine diphosphatase
KW - thiamine diphosphate
KW - thiamine monophosphatase
KW - thiamine monophosphate
KW - thiamine pyrophosphokinase
KW - transformation growth factor
KW - tricarboxylic acid
KW - type 1 diabetes mellitus
KW - type 2 diabetes mellitus
KW - α-ketoglutarate dehydrogenase complex
KW - β-amyloid
KW - γ-PPAR
KW - γ-peroxisome proliferator-actived receptor
SP - 21
EP - 43
JF - Progress in neurobiology
JO - Prog Neurobiol
VL - 108
N2 - Alzheimer's disease (AD) is an age-related devastating neurodegenerative disorder, which severely impacts on the global economic development and healthcare system. Though AD has been studied for more than 100 years since 1906, the exact cause(s) and pathogenic mechanism(s) remain to be clarified. Also, the efficient disease-modifying treatment and ideal diagnostic method for AD are unavailable. Perturbed cerebral glucose metabolism, an invariant pathophysiological feature of AD, may be a critical contributor to the pathogenesis of this disease. In this review, we firstly discussed the features of cerebral glucose metabolism in physiological and pathological conditions. Then, we further reviewed the contribution of glucose transportation abnormality and intracellular glucose catabolism dysfunction in AD pathophysiology, and proposed a hypothesis that multiple pathogenic cascades induced by impaired cerebral glucose metabolism could result in neuronal degeneration and consequently cognitive deficits in AD patients. Among these pathogenic processes, altered functional status of thiamine metabolism and brain insulin resistance are highly emphasized and characterized as major pathogenic mechanisms. Finally, considering the fact that AD patients exhibit cerebral glucose hypometabolism possibly due to impairments of insulin signaling and altered thiamine metabolism, we also discuss some potential possibilities to uncover diagnostic biomarkers for AD from abnormal glucose metabolism and to develop drugs targeting at repairing insulin signaling impairment and correcting thiamine metabolism abnormality. We conclude that glucose metabolism abnormality plays a critical role in AD pathophysiological alterations through the induction of multiple pathogenic factors such as oxidative stress, mitochondrial dysfunction, and so forth. To clarify the causes, pathogeneses and consequences of cerebral hypometabolism in AD will help break the bottleneck of current AD study in finding ideal diagnostic biomarker and disease-modifying therapy.
SN - 1873-5118
UR - https://www.unboundmedicine.com/medline/citation/23850509/Decoding_Alzheimer's_disease_from_perturbed_cerebral_glucose_metabolism:_implications_for_diagnostic_and_therapeutic_strategies_
L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-0082(13)00053-1
DB - PRIME
DP - Unbound Medicine
ER -
