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 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 Apolipoprotein E Genotype-Dependent Nutrigenetic Effects to Prebiotic Inulin for Reducing Risk for Alzheimer's Disease in a Mouse Model

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1197-1197
Author(s):  
Ya-Hsuan Chang ◽  
Jared Hoffman ◽  
Lucille Yanckello ◽  
Scott McCulloch ◽  
Penghui Lin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Apolipoprotein E ◽  
Gut Microbiome ◽  
Apoe Genotype ◽  
Blood Metabolites ◽  
Resonance Spectroscopy ◽  
Metabolic Functions ◽  
Apoe Genotypes

Abstract Objectives Apolipoprotein E ε4 (APOE4) allele is the strongest genetic risk factor for Alzheimer's disease (AD). Cognitively normal APOE4 carriers show an early decline in brain metabolic functions and gut microbiome dysbiosis before the onset of AD compared to APOE3 carriers. Our laboratory previously found that inulin, a prebiotic, is effective to restore metabolic functions and gut microbiome balance, and thus reduce risk for AD in an ApoE4 mouse model. However, whether the responses to the inulin are APOE allele-dependent remains unknown. Therefore, our objective was to identify whether inulin would differently contribute to metabolic and gut microbiome changes due to APOE genotypes. Methods We fed 3-month-old asymptomatic ApoE3 (E3FAD) and ApoE4 (E4FAD) mice prebiotic inulin or cellulose as a control for 4 months (N = 60; Male: Female = 1:1). After 4 months, we used magnetic resonance spectroscopy to measure in vivo brain scyllo-inositol level, a compound that has been demonstrated to inhibit amyloid β aggregation. We collected the fecal samples for gut microbiome sequencing, and cecal and blood samples for metabolomic profiling. Results Inulin induced scyllo-inositol in hippocampus of the brain with a higher level in E4FAD mice. Inulin increased blood metabolites in tryptophan and tyrosine metabolic pathways that enhance nervous system in E3FAD mice. It increased blood metabolites in pentose phosphate pathway and citric acid cycle that support nucleotides and nucleic acids biosynthesis and energy production in E4FAD mice. These alterations in hippocampus and blood showed inulin's impacts on systemic metabolism depending on mouse ApoE genotypes. Inulin enhanced short chain fatty acids in cecum with a greater increase in E3FAD mice. E3FAD mice showed more distinct gut microbiome patterns between inulin and control groups compared to E4FAD mice. Conclusions Inulin-induced systemic metabolism and gut microbiome changes are APOE genotype-dependent. Future studies can design human interventions that may facilitate the guide of personalized nutrition in AD prevention. Funding Sources This research was supported by grants from NIH, NIH/CTSA, and American Federation for Aging Research to A-LL and NIH/NIDDK to JDH and LMY. The 7T ClinScan small animal MRI scanner was funded by the S10 NIH Shared Instrumentation Program Grant.

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 A SERUM PROTEIN SIGNATURE OF APOE GENOTYPES IN CENTENARIANS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S622
Author(s):  
Stefano Monti ◽  
Stefano Monti ◽  
Paola Sebastiani ◽  
Anastasia Gurinovich ◽  
Toshiko Tanaka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Late Onset ◽  
Expression Profiles ◽  
Apoe Genotype ◽  
Cognitive Change ◽  
Serum Proteomics ◽  
Apoe Genotypes ◽  
Protein Signature

Abstract The discovery of treatments to prevent or delay Alzheimer’s disease is a priority. The gene APOE is associated with cognitive change and late onset Alzheimer’s disease, and epidemiological studies have shown that the e_2 allele of APOE has a neuroprotective effect, and it is associated with increased longevity. We correlated APOE genotype data of 222 New England Centenarian Study participants, including 79 centenarians, 84 centenarian offspring and 55 carriers of APOE e_2, with aptamer-based serum proteomics (SomaLogic technology) of 4783 human proteins corresponding to 4137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes, and replicated the signature in 3 independent studies. We show that the protein signature tracks with gene expression profiles in brains of late onset Alzheimer’s disease vs. healthy controls. Finally, we show that seven of these proteins correlate with cognitive function changes. Therefore, targeting APOE e_2 molecularly may preserve cognitive function.

scholarly journals Apolipoprotein E and the CNS Response to Injury

1998 ◽  
Vol 18 (5) ◽  
pp. 465-471 ◽  
Author(s):  
Daniel T. Laskowitz ◽  
Karen Horsburgh ◽  
Allen D. Roses
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Cholesterol Metabolism ◽  
Apoe Genotype ◽  
Acute Injury ◽  
Multifunctional Protein ◽  
Clinical Observations ◽  
Injured Brain ◽  
Antioxidant Effects

Apolipoprotein E (apoE) is a multifunctional protein with an expanding role in the neurobiology of disease. Although originally described in the context of cholesterol metabolism, interest in the neurobiology of apoE has intensified following the association between apoE genotype and risk of developing Alzheimer's disease. Recent clinical observations also suggest that apoE genotype may influence recovery after a variety of neurological insults. Thus, in addition to the study of disease-specific mechanisms by which apoE may modulate susceptibility of developing Alzheimer's disease, there has been an increasing focus on its role in modulating the CNS response to acute injury. Although the neurobiology of apoE in the injured brain remains incompletely defined, there is evidence to suggest neurotrophic, immunomodulatory, and antioxidant effects.

Fragmentation of brain apolipoprotein E (ApoE) and its relevance in Alzheimer's disease

2020 ◽  
Vol 31 (6) ◽  
pp. 589-603 ◽  
Author(s):  
Asiamah Ernest Amponsah ◽  
Baofeng Feng ◽  
Ruiyun Guo ◽  
Wei Zhang ◽  
Jingjing He ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Neurofibrillary Tangles ◽  
Late Onset ◽  
Current Knowledge ◽  
Senile Plaques ◽  
The Elderly ◽  
Pathogenic Potential ◽  
Apoe Protein

AbstractAlzheimer's disease (AD) is a very common cause of dementia in the elderly. It is characterized by progressive amnesia and accretions of neurofibrillary tangles (NFTs) of neurons and senile plaques in the neuropil. After aging, the inheritance of the apolipoprotein E (ApoE) epsilon 4 (ε4) allele is the greatest risk factor for late-onset AD. The ApoE protein is the translated product of the ApoE gene. This protein undergoes proteolysis, and the resulting fragments colocalize with neurofibrillary tangles and amyloid plaques, and for that matter may be involved in AD onset and/or progression. Previous studies have reported the pathogenic potential of various ApoE fragments in AD pathophysiology. However, the pathways activated by the fragments are not fully understood. In this review, ApoE fragments obtained from post-mortem brains and body fluids, cerebrospinal fluid (CSF) and plasma, are discussed. Additionally, current knowledge about the process of fragmentation is summarized. Finally, the mechanisms by which these fragments are involved in AD pathogenesis and pathophysiology are discussed.

Apolipoprotein E Genotype and its Effect on Duration and Severity of Early and Late Onset Alzheimer's Disease

1995 ◽  
Vol 167 (4) ◽  
pp. 533-536 ◽  
Author(s):  
Jennie Norrman ◽  
Anthony J. Brookes ◽  
Celia Yates ◽  
David St Clair
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Apoe Genotype ◽  
Increased Risk ◽  
Apolipoprotein E Genotype

BackgroundThe apolipoprotein E (ApoE) ∊4 allele is associated with an increased risk of senile and probably presenile Alzheimer's disease. It is not yet clear whether the ∊4 allele also influences the duration/rate of progress of illness and the severity of the dementia.MethodWe have retrospectively examined a series of ApoE genotyped presenile and senile autopsy cases of Alzheimer's disease (AD) for length of illness and severity of pathology.ResultsWe find no evidence that ApoE genotype affects the rate of progress of AD, but the degree of pathology at death may be increased.ConclusionIt appears that the rate of progress of AD as a whole is independent of the ApoE genotype.

scholarly journals A CROSS-SECTIONAL ANALYSIS OF APOE GENE POLYMORPHISM AND THE RISK OF COGNITIVE IMPAIRMENTS IN THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE STUDY

2021 ◽  
pp. 1-6
Author(s):  
G. Wang ◽  
D.E. Vance ◽  
W. Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Cognitive Impairments ◽  
Apoe Genotype ◽  
Apoe Gene ◽  
Dependent Manner ◽  
Cross Sectional ◽  
Apoe Genotypes ◽  
Apoe Gene Polymorphism

Background: It is inconclusive on how apolipoprotein epsilon (APOE) gene polymorphism is associated with the risk of having mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Objectives: To investigate how APOE genotype is associated with the risk of MCI or AD using the data collected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants. Methods: A cross-sectional design was used to analyze the baseline data collected from the 1,720 ADNI participants. APOE gene polymorphism was analyzed on how they are related to the risk of cognitive impairments of either MCI or AD using a percent yield (PY) method. Then cognitive functions were compared among six different APOE genotypes using a two-way ANCOVA by controlling possible confounding factors. Results: The prevalence of six APOE genotypes in 1,720 participants is as following: e2/e2 (0.3%), e2/e3 (7.4%), e3/e3 (45.4%), e2/e4 (2%), e3/e4 (35%) and e4/e4 (9.9%). The e2/e2 and e4/e4 genotypes were associated with the lowest and the highest risk respectively for cognitive impairments of either MCI or AD. Further, a worse cognitive diagnosis was associated with an increasing number of APOE e4 allele in a dose dependent manner. Participants with genotype e3/e3 had a better memory measure than those with the genotype of e3/e4. Conclusions: APOE gene polymorphism is associated with different level of risks for cognitive impairments. The heterozygous genotype e3/e4 is associated with a worse memory function compared to the genotype of e3/e3. Further investigations are needed to intervene the cognitive deteriorations in those with at risk APOE genotypes.

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