scholarly journals Determining the Role of ApoE4 in Age-Related Cerebrovascular Decline

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 118-119
Author(s):  
Kate Foley ◽  
Peter Borchian ◽  
Dylan Garceau ◽  
Kevin Kotredes ◽  
Paul Territo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Transcriptional Profiling ◽  
Genetic Risk Factors ◽  
Expression Of Genes ◽  
Age Related ◽  
Age Dependent ◽  
Cerebrovascular Health ◽  
E4 Allele

Abstract Cerebrovascular decline occurs during aging and may be critical during prodromal phases of Alzheimer’s disease (AD). The E4 allele of apolipoprotein E (APOE4) is the greatest genetic risk factor for AD and decreased longevity and studies suggest APOE4 increases risk for age-dependent cerebrovascular damage. To study the relationship between APOE4 and age-related cerebrovascular decline, male and female C57BL/6J (B6) mice carrying combinations of APOE alleles including APOE4 (risk) and APOE3 (neutral), as well as B6 controls were assessed at a variety of ages from 4 to 24 mos for cognitive ability, biometrics and cerebrovascular health including i) PET/MRI using 64Cu-PTSM (perfusion) and 18F-FDG (metabolism), ii) transcriptional profiling and iii) immunofluorescence. Despite no cognitive decline, male APOE4 mice showed hypo-perfusion and hypo-metabolism by 12 mos, while female APOE4 mice showed an uncoupled hyper-perfusion and hypo-metabolism phenotype. Transcriptional profiling showed differential expression of genes involved in regulation of cerebral perfusion, glucose transportation and metabolism in APOE4 mice. An age-dependent blood brain barrier compromise was also apparent in the brains of female APOE4 mice. Physical activity reduces risk for human AD and our data shows exercise improves cerebrovascular health in mice. However, the effects to cerebrovascular health in individuals carrying genetic risk factors such as APOE4 are not known. To determine whether exercise can overcome APOE4-dependent cerebrovascular damage, APOE mice are being exercised from 2-4 and to 2-12 mos. Transcriptional profiling and immunofluorescence will determine whether the benefits of exercise to the cerebrovasculature are modulated by genetic risk factors such as APOE4.

scholarly journals Role of non-Genetic Risk Factors in Exacerbating Alcohol-related organ damage

Alcohol ◽  
2020 ◽  
Vol 87 ◽  
pp. 63-72
Author(s):  
Natalia A. Osna ◽  
Rakesh Bhatia ◽  
Christopher Thompson ◽  
Surinder K. Batra ◽  
Sushil Kumar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Organ Damage

Childhood Porencephaly: Role of Genetic Risk Factors in Familial Trombophilia

1999 ◽  
pp. 310-317
Author(s):  
H. Vielhaber ◽  
O. Debus ◽  
G. Kurlemann ◽  
R. Sträter ◽  
U. Nowak-Göttl
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Genetic Risk Factors

Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population

2018 ◽  
Vol 102 (12) ◽  
pp. 1691-1695 ◽  
Author(s):  
Emma Connolly ◽  
Maedbh Rhatigan ◽  
Aisling M O’Halloran ◽  
Katherine Alyson Muldrew ◽  
Usha Chakravarthy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Disease Progression ◽  
Genetic Risk ◽  
Risk Allele ◽  
Genetic Risk Factors ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Age Related ◽  
Soft Drusen

Background/aimsAge-related macular degeneration (AMD) is estimated to affect 196 million people >50 years old globally. Prevalence of AMD-associated genetic risk factors and rate of disease progression are unknown in Ireland.MethodsPrevalence of AMD-associated genetic risk variants, complement factor H (CFH) rs1061170, age-related maculopathy susceptibility 2 (ARMS2) rs10490924, component 3 (C3) rs2230199, complement factor B (CFB) rs641153 and superkiller viralicidic activity 2-like (SKIV2L) rs429608 and 4-year progression data in a population-representative cohort (The Irish Longitudinal study on Ageing (TILDA)) were assessed. 4473 participants ≥50 years were assessed. 4173 had no disease n=1843; 44% male and n=2330; 56% female, mean age 60±9.0, 300 had AMD n=136; 45% male and n=164; 55% female, mean age 64±9.0. A 4-year follow-up was undertaken with 66% of AMD cases attending. Progression and regression from early to late AMD were measured. Genetic association as indicators of disease and as predictors of progression were assessed by multinomial logistic regression.ResultsOlder age and the presence of CFH and ARMS2 risk alleles are two main risk factors associated with the prevalence of AMD in the TILDA cohort. 23% progressed to a higher grade of AMD. Carriers of CFH risk allele showed a strong association for disease progression. Heterozygosity for ARMS2 risk allele predicted progression to late AMD. 75% of those who progressed from early to late disease had soft drusen and hyperpigmentation at baseline.ConclusionsThe prevalence of risk-associated genes and 4-year progression rates of AMD in this Ireland cohort are comparable with other Caucasian populations. CFH Y402H is associated with disease progression, with soft drusen and hyperpigmentation as high-risk features.

Genetic Risk Factors for Arterial Thrombosis and Inflammation

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 442-444 ◽  
Author(s):  
David Ginsburg
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Arterial Thrombosis ◽  
Rapid Development ◽  
Genetic Risk Factors ◽  
Developed Countries ◽  
Inflammatory Factor ◽  
Current State ◽  
Molecular Pathophysiology

Abstract Arterial thrombosis is a central pathologic mechanism contributing to myocardial infarction and stroke, together the leading causes of death in developed countries. This article reviews the current state of knowledge concerning the role of inherited variation in hemostatic and inflammatory factor genes in determining the risk of arterial thrombosis/ischemic heart disease. Despite considerable progress in identifying important genetic risk factors underlying predisposition to venous thrombosis, the genetic factors contributing to the risk for arterial thrombosis remain largely unknown. However, the rapid development of powerful new genomic resources should facilitate considerably more sophisticated analyses, leading to novel insight into the molecular pathophysiology of this important set of human diseases.

scholarly journals Puzzling role of genetic risk factors in human longevity: “risk alleles” as pro-longevity variants

2015 ◽  
Vol 17 (1) ◽  
pp. 109-127 ◽  
Author(s):  
Svetlana Ukraintseva ◽  
Anatoliy Yashin ◽  
Konstantin Arbeev ◽  
Alexander Kulminski ◽  
Igor Akushevich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Human Longevity ◽  
Longevity Risk ◽  
Risk Alleles

scholarly journals A Levee to the Flood: Pre-injury Neuroinflammation and Immune Stress Influence Traumatic Brain Injury Outcome

2022 ◽  
Vol 13 ◽  
Author(s):  
Samuel Houle ◽  
Olga N. Kokiko-Cochran
Keyword(s):  
Risk Factors ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Genetic Risk ◽  
Traumatic Injury ◽  
Genetic Risk Factors ◽  
Post Injury ◽  
Immune Stress ◽  
Age Related

Increasing evidence demonstrates that aging influences the brain's response to traumatic brain injury (TBI), setting the stage for neurodegenerative pathology like Alzheimer's disease (AD). This topic is often dominated by discussions of post-injury aging and inflammation, which can diminish the consideration of those same factors before TBI. In fact, pre-TBI aging and inflammation may be just as critical in mediating outcomes. For example, elderly individuals suffer from the highest rates of TBI of all severities. Additionally, pre-injury immune challenges or stressors may alter pathology and outcome independent of age. The inflammatory response to TBI is malleable and influenced by previous, coincident, and subsequent immune insults. Therefore, pre-existing conditions that elicit or include an inflammatory response could substantially influence the brain's ability to respond to traumatic injury and ultimately affect chronic outcome. The purpose of this review is to detail how age-related cellular and molecular changes, as well as genetic risk variants for AD affect the neuroinflammatory response to TBI. First, we will review the sources and pathology of neuroinflammation following TBI. Then, we will highlight the significance of age-related, endogenous sources of inflammation, including changes in cytokine expression, reactive oxygen species processing, and mitochondrial function. Heightened focus is placed on the mitochondria as an integral link between inflammation and various genetic risk factors for AD. Together, this review will compile current clinical and experimental research to highlight how pre-existing inflammatory changes associated with infection and stress, aging, and genetic risk factors can alter response to TBI.

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