scholarly journals The Synergistic Effects of APOE Genotype and Obesity on Alzheimer’s Disease Risk

2018 ◽  
Vol 20 (1) ◽  
pp. 63 ◽  
Author(s):  
Nahdia Jones ◽  
G. Rebeck
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Cognitive Deficits ◽  
Disease Risk ◽  
Synergistic Effects ◽  
Apoe Genotype ◽  
Global Epidemic ◽  
Underlying Mechanisms ◽  
Apoe Genotypes

The APOE gene has three common alleles—E2, E3, and E4, with APOE4 being the strongest genetic risk factor for developing Alzheimer’s Disease (AD). Obesity is a global epidemic and contributes to multiple metabolic problems. Obesity is also a risk factor for cognitive decline. Here, we review the effects of APOE4 and obesity on cognition and AD development, independently and together. We describe studies that have associated APOE4 with cognitive deficits and AD, as well as studies that have associated obesity to cognitive deficits and AD. We then describe studies that have examined the effects of obesity and APOE genotypes together, with a focus on APOE4 and high fat diets. Both human studies and rodent models have contributed to understanding the effects of obesity on the different APOE genotypes, and we outline possible underlying mechanisms associated with these effects. Data across approaches support a model in which APOE4 and obesity combine for greater detrimental effects on metabolism and cognition, in ways that are influenced by both age and sex.

scholarly journals Associations between depression, sleep disturbance, and apolipoprotein E in the development of Alzheimer's disease: dementia

2016 ◽  
Vol 28 (9) ◽  
pp. 1409-1424 ◽  
Author(s):  
Shanna L. Burke ◽  
Peter Maramaldi ◽  
Tamara Cadet ◽  
Walter Kukull
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Sleep Disturbance ◽  
Reference Group ◽  
Synergistic Effects ◽  
Apoe Genotype ◽  
The Elderly ◽  
Prodromal Symptom ◽  
Apoe Genotypes

ABSTRACTBackground:Alzheimer's disease (AD) is a neurodegenerative brain disease that causes cognitive impairment and dementia. Within the US, AD is the most common form of dementia in the elderly, affecting 1 in 10 people over the age of 65. Sleep disturbance has been called a “public health epidemic” and, like depression, is a prodromal symptom of AD but may also contribute to the risk of developing AD. It was hypothesized that sleep disturbance, depression, and the apolipoprotein E (APOE) genotype increase the likelihood of AD.Methods:Utilizing data from the National Alzheimer's Coordinating Center, information from evaluations of 11,453 cognitively asymptomatic participants was analyzed. Survival analysis was used to explore the independent relationships between depression, sleep disturbance, and APOE genotypes with eventual AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic effects of psychosocial factors as moderated by APOE genotypes.Results:This study reinforced the association between APOE and AD. The hazard of developing AD was eight times higher for those with recent depression and the Ɛ4 homozygote (HR = 8.15 [3.70–17.95]). Among Ɛ4 carriers with clinician-verified depression, the hazard was ten times that of the reference group (HR = 10.11 [4.43–23.09]). The hazard for Ɛ4 carriers reporting sleep disturbance was almost 7 times greater than the reference group (HR = 6.79 [2.38–19.37]).Conclusion:Findings suggest that sleep disturbance, depression, and APOE Ɛ4 genotype are associated with AD during follow-up evaluations among a group of initially cognitively asymptomatic participants. This study contributes to the literature base exploring an increased hazard or risk of AD due to potential modifiable risk factors as well as genetic biomarkers, such as APOE.

scholarly journals Dendritic/Post-synaptic Tau and Early Pathology of Alzheimer’s Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Xiaomin Yin ◽  
Chenhao Zhao ◽  
Yanyan Qiu ◽  
Zheng Zhou ◽  
Junze Bao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Dendritic Spines ◽  
Synergistic Effects ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Functional Deficits ◽  
Underlying Mechanisms ◽  
Oligomeric Forms

Microtubule-associated protein tau forms insoluble neurofibrillary tangles (NFTs), which is one of the major histopathological hallmarks of Alzheimer’s disease (AD). Many studies have demonstrated that tau causes early functional deficits prior to the formation of neurofibrillary aggregates. The redistribution of tau from axons to the somatodendritic compartment of neurons and dendritic spines causes synaptic impairment, and then leads to the loss of synaptic contacts that correlates better with cognitive deficits than amyloid-β (Aβ) aggregates do in AD patients. In this review, we discuss the underlying mechanisms by which tau is mislocalized to dendritic spines and contributes to synaptic dysfunction in AD. We also discuss the synergistic effects of tau and oligomeric forms of Aβ on promoting synaptic dysfunction in AD.

Race-Related Association between APOE Genotype and Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-10
Author(s):  
Wei Qin ◽  
Wenwen Li ◽  
Qi Wang ◽  
Min Gong ◽  
Tingting Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Black People ◽  
Late Onset ◽  
Meta Analysis ◽  
Group Analysis ◽  
Apoe Genotype ◽  
Cochrane Library ◽  
Data Sets ◽  
Apoe Genotypes

Background: The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective: This study aims to determine how race and APOE genotype affect the risks for AD. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ between races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.

scholarly journals Alzheimer's Disease Risk Factor Pyk2 Mediates Amyloid-β-Induced Synaptic Dysfunction and Loss

2018 ◽  
Vol 39 (4) ◽  
pp. 758-772 ◽  
Author(s):  
Santiago V. Salazar ◽  
Timothy O. Cox ◽  
Suho Lee ◽  
A. Harrison Brody ◽  
Annabel S. Chyung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Disease Risk Factor

scholarly journals Alzheimer’s disease risk factor mutations in patients diagnosed with Creutzfelt‐Jakob disease

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Eva Bagyinszky ◽  
Lindsay A. Farrer ◽  
John Farrell ◽  
Giau Van Vo ◽  
KyuHwan Shim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Disease Risk Factor ◽  
Jakob Disease

scholarly journals PICALM Rescues Endocytic Defects Caused by the Alzheimer’s Disease Risk Factor APOE4

Cell Reports ◽  
2020 ◽  
Vol 33 (1) ◽  
pp. 108224
Author(s):  
Priyanka Narayan ◽  
Grzegorz Sienski ◽  
Julia M. Bonner ◽  
Yuan-Ta Lin ◽  
Jinsoo Seo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Disease Risk Factor

scholarly journals Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3842
Author(s):  
Harvey R. Fernandez ◽  
Ashima Varma ◽  
Sarah A. Flowers ◽  
George William Rebeck
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Cancer Chemotherapy ◽  
Apoe Genotype ◽  
Brain Barrier ◽  
Blood Brain

Cancer related cognitive impairment (CRCI) is a serious impairment to maintaining quality of life in cancer survivors. Cancer chemotherapy contributes to this condition through several potential mechanisms, including damage to the blood brain barrier, increases in oxidative stress and inflammation in the brain, and impaired neurogenesis, each of which lead to neuronal dysfunction. A genetic predisposition to CRCI is the E4 allele of the Apolipoprotein E gene (APOE), which is also the strongest genetic risk factor for Alzheimer’s disease. In normal brains, APOE performs essential lipid transport functions. The APOE4 isoform has been linked to altered lipid binding, increased oxidative stress and inflammation, reduced turnover of neural progenitor cells, and impairment of the blood brain barrier. As chemotherapy also affects these processes, the influence of APOE4 on CRCI takes on great significance. This review outlines the main areas where APOE genotype could play a role in CRCI. Potential therapeutics based on APOE biology could mitigate these detrimental cognitive effects for those receiving chemotherapy, emphasizing that the APOE genotype could help in developing personalized cancer treatment regimens.

Alzheimer's disease risk factor complement receptor 1 is associated with depression

2012 ◽  
Vol 510 (1) ◽  
pp. 6-9 ◽  
Author(s):  
Gillian Hamilton ◽  
Kathryn L. Evans ◽  
Donald J. MacIntyre ◽  
Ian J. Deary ◽  
Anna Dominiczak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Complement Receptor ◽  
Disease Risk Factor ◽  
Complement Receptor 1
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