Diabetes as a risk factor for Alzheimer's disease in the Middle East and its shared pathological mediators.
AAV, Adeno-associated virus
ABCA1, ATP binding cassette subfamily A member 1
AD, Alzheimer’s disease
ADAMTS9, ADAM Metallopeptidase With Thrombospondin Type 1 Motif 9
AGPAT1, 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha
Alzheimer’s disease
Anti-diabetic drugs
ApoE, Apolipoprotein E
Arab population
Aβ, Amyloid-beta
BACE1, Beta-secretase 1
BBB, Blood-Brain Barrier
BMI, Body mass index
CALR, calreticulin gene
CIP2A, Cancerous Inhibitor Of Protein Phosphatase 2A
COX-2, Cyclooxygenase 2
CSF, Cerebrospinal fluid
DM, Diabetes mellitus
DUSP9, Dual Specificity Phosphatase 9
Diabetes mellitus
ECE-1, Endotherin converting enzyme 1
FDG-PET, Fluorodeoxyglucose- positron emission tomography
FRMD4A, FERM Domain Containing 4A
FTO, Fat Mass and Obesity Associated Gene
GLP-1, Glucagon like peptide
GNPDA2, Glucosamine-6-phosphate deaminase 2
GSK-3β, Glycogen synthase kinase 3 beta
IDE, Insulin degrading enzyme
IGF-1, Insulin-like growth factor 1
IR, Insulin receptor
IR, Insulin resistance
Insulin signaling
LPA, Lipophosphatidic acid
MC4R, Melanocortin 4 receptor
MCI, Myocardial infarction
MENA, Middle East North African
MG-H1, Methylglyoxal-hydroimidazolone isomer trifluoroactic acid salt
MRI, Magnetic resonance imaging
NDUFS3, NADH:Ubiquinone Oxidoreductase Core Subunit S3
NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells
NFT, Neurofibrillary tangles
NOTCH4, Neurogenic locus notch homolog protein 4
PI3K, Phosphoinositide-3
PP2A, Protein phosphatase 2
PPAR-γ2, Peroxisome proliferator-activated receptor gamma 2
Pit-PET, Pittsburgh compound B- positron emission tomography
RAB1A, Ras-related protein 1A
SORT, Sortilin
STZ, Streptozotocin
T1DM, Type 1 Diabetes Mellitus
T2DM, Type 2 Diabetes Mellitus
TCF7L2, Transcription Factor 7 Like 2
TFAP2B, Transcription Factor AP-2 Beta
Journal
Saudi journal of biological sciences
ISSN: 1319-562X
Titre abrégé: Saudi J Biol Sci
Pays: Saudi Arabia
ID NLM: 101543796
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
28
10
2019
revised:
14
12
2019
accepted:
18
12
2019
entrez:
27
3
2020
pubmed:
27
3
2020
medline:
27
3
2020
Statut:
ppublish
Résumé
The incidence of Alzheimer's disease (AD) has risen exponentially worldwide over the past decade. A growing body of research indicates that AD is linked to diabetes mellitus (DM) and suggests that impaired insulin signaling acts as a crucial risk factor in determining the progression of this devastating disease. Many studies suggest people with diabetes, especially type 2 diabetes, are at higher risk of eventually developing Alzheimer's dementia or other dementias. Despite nationwide efforts to increase awareness, the prevalence of Diabetes Mellitus (DM) has risen significantly in the Middle East and North African (MENA) region which might be due to rapid urbanization, lifestyle changes, lack of physical activity and rise in obesity. Growing body of evidence indicates that DM and AD are linked because both conditions involve impaired glucose homeostasis and altered brain function. Current theories and hypothesis clearly implicate that defective insulin signaling in the brain contributes to synaptic dysfunction and cognitive deficits in AD. In the periphery, low-grade chronic inflammation leads to insulin resistance followed by tissue deterioration. Thus insulin resistance acts as a bridge between DM and AD. There is pressing need to understand on how DM increases the risk of AD as well as the underlying mechanisms, due to the projected increase in age related disorders. Here we aim to review the incidence of AD and DM in the Middle East and the possible link between insulin signaling and ApoE carrier status on Aβ aggregation, tau hyperphosphorylation, inflammation, oxidative stress and mitochondrial dysfunction in AD. We also critically reviewed mutation studies in Arab population which might influence DM induced AD. In addition, recent clinical trials and animal studies conducted to evaluate the efficiency of anti-diabetic drugs have been reviewed.
Identifiants
pubmed: 32210695
doi: 10.1016/j.sjbs.2019.12.028
pii: S1319-562X(19)30328-6
pmc: PMC6997863
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
736-750Informations de copyright
© 2019 Published by Elsevier B.V. on behalf of King Saud University.
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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