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https://www.readbyqxmd.com/read/29776682/the-impact-of-apolipoprotein-e-alleles-on-cognitive-performance-in-patients-with-parkinson-s-disease
#1
Anna Pierzchlińska, Monika Białecka, Mateusz Kurzawski, Jarosław Sławek
Apolipoprotein E (ApoE) is a vital component of several lipoproteins and plays a major role in lipid metabolism. APOE gene comprises of three alleles determined by two single nucleotide polymorphisms (rs429358 and rs7412) resulting in the protein isoforms, among which ApoE4 is a confirmed risk factor for Alzheimer's Disease. However, the impact of APOE genotypes on Parkinson's Disease Dementia (PDD) is still inconclusive. The PDD diagnostic criteria are very inconsistent, and could be complemented with genetic factors...
May 5, 2018: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29761124/progranulin-levels-in-blood-in-alzheimer-s-disease-and-mild-cognitive-impairment
#2
Yonatan A Cooper, Daniel Nachun, Deepika Dokuru, Zhongan Yang, Anna M Karydas, Ginette Serrero, Binbin Yue, Adam L Boxer, Bruce L Miller, Giovanni Coppola
Objective: Changes in progranulin ( GRN ) expression have been hypothesized to alter risk for Alzheimer's disease (AD). We investigated the relationship between GRN expression in peripheral blood and clinical diagnosis of AD and mild cognitive impairment (MCI). Methods: Peripheral blood progranulin gene expression was measured, using microarrays from Alzheimer's ( n = 186), MCI ( n = 118), and control ( n = 204) subjects from the University of California San Francisco Memory and Aging Center (UCSF-MAC) and two independent published series (AddNeuroMed and ADNI)...
May 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29743204/apoe-isoforms-and-carboxyl-terminal-truncated-apoe4-forms-affect-neuronal-bace1-levels-and-a%C3%AE-production-independently-of-their-cholesterol-efflux-capacity
#3
Ioannis Dafnis, Christina Raftopoulou, Christina Mountaki, Evgenia Megalou, Vassilis I Zannis, Angeliki Chroni
The beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) initiates the production of amyloid-beta peptide (Aβ) which is central to the pathogenesis of Alzheimer's disease (AD). Changes in brain cholesterol homeostasis have been suggested to affect Aβ metabolism. Cholesterol homeostasis is maintained in the brain by apolipoprotein E (apoE). The apoE4 isoform constitutes the major risk factor for AD. Here, we investigated the effect of apoE forms on Aβ generation and on BACE1 levels. We also examined the potential involvement in these processes of cholesterol transporters ABCG1 and ABCG4 or the lipoprotein receptor SR-BI that are implicated in cholesterol efflux to apoE...
May 9, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29740579/the-role-of-genetics-in-advancing-precision-medicine-for-alzheimer-s-disease-a-narrative-review
#4
REVIEW
Yun Freudenberg-Hua, Wentian Li, Peter Davies
Alzheimer's disease (AD) is the most common type of dementia, which has a substantial genetic component. AD affects predominantly older people. Accordingly, the prevalence of dementia has been rising as the population ages. To date, there are no effective interventions that can cure or halt the progression of AD. The only available treatments are the management of certain symptoms and consequences of dementia. The current state-of-the-art medical care for AD comprises three simple principles: prevent the preventable, achieve early diagnosis, and manage the manageable symptoms...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29732606/influence-of-6-genetic-variants-on-the-efficacy-of-statins-in-patients-with-dyslipidemia
#5
Ruth Cano-Corres, Beatriz Candás-Estébanez, Ariadna Padró-Miquel, Marta Fanlo-Maresma, Xavier Pintó, Pedro Alía-Ramos
BACKGROUND: Patients with dyslipidemia are often treated with statins to reduce lipids and hence cardiovascular risk, but treatment response is variable, partly due to genetic factors. METHODS: We studied the influence of 6 gene variants (APOE c.526C > T (APOE2), APOE c.388T > C (APOE4), SLCO1B1 c.521T > C, CYP3A4 c.-392G > A, HMGCR c.1564-106A > G, and LPA c.3947 + 467T > C) on statin efficacy assessing 2 indicators: the percent reduction in total cholesterol (TC) and non-HDL cholesterol (non-HDL), as well as the achievement of therapeutic goals...
May 7, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29729672/association-of-oily-fish-intake-sex-age-bmi-and-apoe-genotype-with-plasma-long-chain-n-3-fatty-acid-composition
#6
Helena L Fisk, Michael Irvine, Elizabeth A Miles, Georg Lietz, John C Mathers, Chris J Packard, Christopher K Armah, Bettina M Kofler, Peter J Curtis, Anne M Minihane, Philip C Calder
n-3 Fatty acids are associated with better cardiovascular and cognitive health. However, the concentration of EPA, DPA and DHA in different plasma lipid pools differs and factors influencing this heterogeneity are poorly understood. Our aim was to evaluate the association of oily fish intake, sex, age, BMI and APOE genotype with concentrations of EPA, DPA and DHA in plasma phosphatidylcholine (PC), NEFA, cholesteryl esters (CE) and TAG. Healthy adults (148 male, 158 female, age 20-71 years) were recruited according to APOE genotype, sex and age...
May 6, 2018: British Journal of Nutrition
https://www.readbyqxmd.com/read/29710700/severity-related-increase-and-cognitive-correlates-of-serum-vegf-levels-in-alzheimer-s-disease-apoe4-carriers
#7
X Anton Alvarez, Irene Alvarez, Manuel Aleixandre, Carlos Linares, Dafin Muresanu, Stefan Winter, Herbert Moessler
Vascular endothelial growth factor (VEGF) is an angioneurin involved in the regulation of vascular and neural functions relevant for the pathophysiology of Alzheimer's disease (AD), but the influence of AD severity and ApoE4 status on circulating VEGF and its relationship with cognition has not been investigated. We assessed serum VEGF levels and cognitive performance in AD, amnestic mild cognitive impairment (MCI), and control subjects. VEGF levels were higher in AD patients than in MCI cases and controls (p < 0...
April 25, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29706312/metabolic-syndrome-marks-early-risk-for-cognitive-decline-with-apoe4-gene-variation-a-case-study
#8
Dawson Brown, Kelly J Gibas
A vast amount of research has been done on the APOE4 genetic marker for Alzheimer's disease (AD), but its connection to metabolic processes associated with peripheral insulin resistance and cerebral glucose metabolism is still relatively unknown. The APOE4 allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, particularly in individuals who have inherited two copies of the gene (Zhao et al., 2017). In this case study, a 38 year old male with metabolic syndrome (MetS), the APOE4 gene, early stage memory problems and a family history of Alzheimer's Disease (AD) was placed on a ketogenic diet combined with high intensity interval training (HIIT) for 10 weeks...
April 20, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29705945/could-alzheimer-s-disease-originate-in-the-periphery-and-if-so-how-so
#9
REVIEW
Gerwyn Morris, Michael Berk, Michael Maes, Basant K Puri
The classical amyloid cascade model for Alzheimer's disease (AD) has been challenged by several findings. Here, an alternative molecular neurobiological model is proposed. It is shown that the presence of the APOE ε4 allele, altered miRNA expression and epigenetic dysregulation in the promoter region and exon 1 of TREM2, as well as ANK1 hypermethylation and altered levels of histone post-translational methylation leading to increased transcription of TNFA, could variously explain increased levels of peripheral and central inflammation found in AD...
April 29, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29704008/impact-of-late-onset-alzheimer-s-genetic-risk-factors-on-beta-amyloid-endocytic-production
#10
REVIEW
Cláudia Guimas Almeida, Farzaneh Sadat Mirfakhar, Catarina Perdigão, Tatiana Burrinha
The increased production of the 42 aminoacids long beta-amyloid (Aβ42) peptide has been established as a causal mechanism of the familial early onset Alzheimer's disease (AD). In contrast, the causal mechanisms of the late-onset AD (LOAD), that affects most AD patients, remain to be established. Indeed, Aβ42 accumulation has been detected more than 30 years before diagnosis. Thus, the mechanisms that control Aβ accumulation in LOAD likely go awry long before pathogenesis becomes detectable. Early on, APOE4 was identified as the biggest genetic risk factor for LOAD...
April 27, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29689315/stress-as-risk-factor-for-alzheimer-s-disease
#11
REVIEW
Alessandra Caruso, Ferdinando Nicoletti, Dalila Mango, Amira Saidi, Rosamaria Orlando, Sergio Scaccianoce
Prolonged stress predisposes susceptible individuals to a number of physiological disorders including cardiovascular disease, obesity and gastrointestinal disorders, as well as psychiatric and neurodegenerative disorders. Preclinical studies have suggested that manipulation of the glucocorticoid milieu can trigger cellular, molecular and behavioral derangement resembling the hallmarks of Alzheimer's Disease (AD). For example, stress or glucocorticoid administration can increase amyloid ß precursor protein and tau phosphorylation which are involved in synaptic dysfunction and neuronal death associated with AD...
April 21, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29682502/frontiers-of-complex-disease-mechanisms-membrane-surface-tension-may-link-genotype-to-phenotype-in-glaucoma
#12
Howard R Petty
Although many monogenic diseases are understood based upon structural changes of gene products, less progress has been made concerning polygenic disease mechanisms. This article presents a new interdisciplinary approach to understand complex diseases, especially their genetic polymorphisms. I focus upon primary open angle glaucoma (POAG). Although elevated intraocular pressure (IOP) and oxidative stress are glaucoma hallmarks, the linkages between these factors and cell death are obscure. Reactive oxygen species (ROS) promote the formation of oxidatively truncated phosphoglycerides (OTP), free fatty acids, lysophosphoglycerides, oxysterols, and other chemical species that promote membrane disruption and decrease membrane surface tension...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29679801/metabolic-control-apoe-genotypes-and-dyslipidemia-in-children-adolescents-and-young-adults-with-type-1-diabetes
#13
Maddalena Macedoni, Tinka Hovnik, Emil Plesnik, Primoz Kotnik, Natasa Bratina, Tadej Battelino, Urh Groselj
BACKGROUND AND AIMS: Limited data is available on the factors influencing the lipid profiles and the prevalence of dyslipidemia in children, adolescents and young adults with type 1 diabetes. We aimed at assessing the influences of metabolic control and ApoE genotypes on lipid profiles and the prevalence of dyslipidemia in children, adolescents and young adults with type 1 diabetes. METHODS: Children, adolescents and young adults with type 1 diabetes from our nationwide cohort attending the annual check-up were prospectively included...
April 12, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29678753/human-apolipoprotein-e-genotype-differentially-affects-olfactory-behavior-and-sensory-physiology-in-mice
#14
Brett S East, Gloria Fleming, Kathy Peng, Jonas K Olofsson, Efrat Levy, Paul M Mathews, Donald A Wilson
Apolipoprotein E (ApoE) is an important lipid carrier in both the periphery and the brain. The ApoE ε4 allele (ApoE4) is the single most important genetic risk-factor for Alzheimer's disease (AD) while the ε 2 allele (ApoE2) is associated with a lower risk of AD-related neurodegeneration compared to the most common variant, ε 3 (ApoE3). ApoE genotype affects a variety of neural circuits; however, the olfactory system appears to provide early biomarkers of ApoE genotype effects. Here, we directly compared olfactory behavior and olfactory system physiology across all three ApoE genotypes in 6-month- and 12-month-old mice with targeted replacement for the human ApoE2, ApoE3, or ApoE4 genes...
April 17, 2018: Neuroscience
https://www.readbyqxmd.com/read/29660940/age-dependent-changes-to-sphingolipid-balance-in-the-human-hippocampus-are-gender-specific-and-may-sensitize-to-neurodegeneration
#15
Timothy A Couttas, Nupur Kain, Collin Tran, Zac Chatterton, John B Kwok, Anthony S Don
The greatest risk factor for developing Alzheimer's disease (AD) is aging. The major genetic risk factor for AD is the ɛ4 allele of the APOE gene, encoding the brain's major lipid transport protein, apolipoprotein E (ApoE). The research community is yet to decipher why the ApoE4 variant pre-disposes to AD, and how aging causes the disease. Studies have shown deregulated levels of sphingolipids, including decreased levels of the neuroprotective signaling lipid sphingosine 1-phosphate (S1P), and increased ceramide content, in brain tissue and serum of people with pre-clinical or very early AD...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29658078/analysis-of-the-role-of-carriership-of-polymorphic-genotypes-of-esr1-enos-and-apoe4-genes-in-the-development-of-arterial-hypertension-in-men
#16
O V Dolgikh, N V Zaitseva, A E Nosov, A V Krivtsov, D G Dianova, O A Kazakova, E A Otavina, I N Alikina
We studied the role of the carrier status for polymorphic loci of genes encoding estrogen receptors (ESR1), endothelial NO synthase (eNOS), and apolipoprotein E (APOE4) and products of their expression nitrogen oxide (NO) and apolipoprotein (ApoE) in the development of arterial hypertension in men. Conventionally healthy volunteers and 149 men with clinical manifestations of stage I-II arterial hypertension were examined. In men with arterial hypertension, the frequency of minor allele A of ESR1 gene was higher (27...
April 16, 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29623835/apoe4-may-be-a-promising-target-for-treatment-of-coronary-heart-disease-and-alzheimer-s-disease
#17
Wei Chen, Fengzhong Jin, Guihua Cao, Rong Mei, Yayun Wang, Pan Long, Xiaoming Wang, Wei Ge
Alzheimer disease (AD) is most common neurodegenerative disorder of dementia, as we all know, ApoE4 is the greatest genetic risk factor of late-onset Alzheimer&#039;s disease (LOAD). Coronary heart disease (CHD) lead to one-fourth of all deaths in industrialized countries, it is reported that ApoE4 increases the risk of coronary heart disease as well. Furthermore, evidence show that coronary heart disease also increases the incidence of Alzheimer's disease. Whether ApoE4 is a bridge connecting AD with CHD or not? And what are the special mechanism and therapeutic methods? Researchers found that cholesterol metabolic disorder is common causes and risk factors of AD and CHD...
April 5, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29618365/apolipoprotein-e4-impairs-spontaneous-blood-brain-barrier-repair-following-traumatic-brain-injury
#18
Bevan S Main, Sonia Villapol, Stephanie S Sloley, David J Barton, Maia Parsadanian, Chinyere Agbaegbu, Kathryn Stefos, Mondona S McCann, Patricia M Washington, Olga C Rodriguez, Mark P Burns
BACKGROUND: Traumatic Brain Injury (TBI) is a major cause of disability and mortality, to which there is currently no comprehensive treatment. Blood Brain Barrier (BBB) dysfunction is well documented in human TBI patients, yet the molecular mechanisms that underlie this neurovascular unit (NVU) pathology remains unclear. The apolipoprotein-E (apoE) protein has been implicated in controlling BBB integrity in an isoform dependent manner, via suppression of Cyclophilin A (CypA)-Matrix metallopeptidase-9 (MMP-9) signaling cascades, however the contribution of this pathway in TBI-induced BBB permeability is not fully investigated...
April 4, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29607445/a-review-on-the-general-stability-of-mood-disorder-diagnoses-along-the-lifetime
#19
REVIEW
Diego de la Vega, Ana Piña, Francisco J Peralta, Sam A Kelly, Lucas Giner
PURPOSE OF REVIEW: The purpose of this review is to review the most recent literature regarding diagnostic stability of mood disorders, focusing on epidemiological, clinical-psychopathological, and neurobiological data for unipolar and bipolar affective disorders. RECENT FINDINGS: Unipolar depression follows a chronic course in at least half of all cases and presents a considerable diagnostic stability across all age ranges. Studies using latent class analysis are allowing improved profiling of depressive subtypes and assessment of their prevalence...
April 2, 2018: Current Psychiatry Reports
https://www.readbyqxmd.com/read/29600962/targeting-the-accomplice-to-thwart-the-culprit-a-new-target-for-the-prevention-of-amyloid-deposition
#20
David R Borchelt
Inheritance of the E4 allele of the apolipoprotein E gene (APOE4) substantially increases the risk of developing late-onset Alzheimer disease (AD). A large body of evidence has firmly established a role for apoE in modulating the risk of developing the amyloid plaque pathology that is pathognomonic for AD. In this issue of the JCI, Liao and colleagues discovered that antibodies against a nonlipidated form of apoE4 are highly effective in delaying the deposition of amyloid β (Aβ) peptides in mouse models of AD pathology...
May 1, 2018: Journal of Clinical Investigation
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