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https://www.readbyqxmd.com/read/28744113/apolipoprotein-%C3%AE%C2%B57-allele-in-memory-complaints-insights-through-protein-structure-prediction
#1
Young Chul Youn, Yong Kwan Lim, Su-Hyun Han, Vo Van Giau, Mi-Kyung Lee, Kwang-Yeol Park, SangYun Kim, Eva Bagyinszky, Seong Soo A An, Hye Ryoun Kim
PURPOSE: APOE ε7 gene is a rare mutant form of APOE ε3. The mutation occurs in the lipid-binding domain of APOE. Based on the protein's structure, APOE ε7 is expected to function in lipid and β-amyloid metabolism, similar to APOE ε4. However, unlike that for APOE ε4, the mechanisms responsible for Alzheimer's disease (AD) cases associated with APOE ε7 expression have not been elucidated. The present study aims to investigate the association between APOE ε7 expression and cognitive impairment...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28734792/genetic-factors-of-cervical-spondylotic-myelopathy-a-systemic-review
#2
REVIEW
Guohua Wang, Yong Cao, Tianding Wu, Chunyue Duan, Jianhuang Wu, Jianzhong Hu, Hongbin Lu
BACKGROUND: Cervical spondylotic myelopathy (CSM) is a degenerative disorder of the neck. Recent studies have reported the roles of single nucleotide polymorphisms and abnormal gene expression in the etiology and development of CSM. However, a systemic review of these findings is currently unavailable. METHODS: A systemic review of genetic factors of CSM was conducted through searching PubMed and EMbase databases. A total of 9 studies were included in this study, which included 8 genes: brain derived neurotrophic factor (BDNF), osteopontin (OPN), bone morphogenic protein (BMP) 4, collagen IX, vitamin D receptor (VDR), apolipoprotein E (ApoE), hypoxia-inducible factor α (HIF-1α), and cyclooxygenase 2 (COX-2)...
July 19, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28731444/the-relationship-of-brain-amyloid-load-and-apoe-status-to-regional-cortical-thinning-and-cognition-in-the-adni-cohort
#3
Chunfei Li, David A Loewenstein, Ranjan Duara, Mercedes Cabrerizo, Warren Barker, Malek Adjouadi
BACKGROUND: Both amyloid (Aβ) load and APOE4 allele are associated with neurodegenerative changes in Alzheimer's disease (AD) prone regions and with risk for cognitive impairment. OBJECTIVE: To evaluate the unique and independent contribution of APOE4 allele status (E4+∖E4-), Aβ status (Amy+∖Amy-), and combined APOE4 and Aβ status on regional cortical thickness (CoTh) and cognition among participants diagnosed as cognitively normal (CN, n = 251), early mild cognitive impairment (EMCI, n = 207), late mild cognitive impairment (LMCI, n = 196), and mild AD (n = 162) from the ADNI...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731260/transcriptional-regulation-of-app-by-apoe-to-boldly-go-where-no-isoform-has-gone-before-apoe-app-transcription-and-ad-hypothesised-mechanisms-and-existing-knowledge-gaps
#4
REVIEW
Liying Corinne Lee, Michele Q L Goh, Edward H Koo
Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti-amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β-protein and its precursor, the amyloid precursor protein (APP) are but a part of the disease cascade. Further, risk of AD can be modulated by a number of factors, the most impactful being the ɛ4 isoform of apolipoprotein E (apoE)...
July 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28720530/downregulation-of-protein-phosphatase-2a-by-apolipoprotein-e-implications-for-alzheimer-s-disease
#5
Veena Theendakara, Dale E Bredesen, Rammohan V Rao
The apolipoprotein E ε4 allele is the single most important genetic risk factor associated with Alzheimer's disease (AD). Tau phosphorylation and hyperphosphorylation is an underlying feature of AD and is regulated by specific kinases and phosphatases. Among phosphatases, protein phosphatase 2A (PP2A) is the principal tau dephosphorylating enzyme in the brain. Several abnormalities of PP2A have been reported in AD, including among others decreased protein levels of PP2A, decreased mRNA and protein levels of the catalytic subunit PP2AC and variable regulatory B subunits and reduced methylation of the catalytic subunit, all of which results in disruption of the PP2A phosphatase activity...
July 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28716532/multivariate-analyses-of-peripheral-blood-leukocyte-transcripts-distinguish-alzheimer-s-parkinson-s-control-and-those-at-risk-for-developing-alzheimer-s
#6
Elaine Delvaux, Diego Mastroeni, Jennifer Nolz, Nienwen Chow, Marwan Sabbagh, Richard J Caselli, Eric M Reiman, Frederick J Marshall, Paul D Coleman
The need for a reliable, simple, and inexpensive blood test for Alzheimer's disease (AD) suitable for use in a primary care setting is widely recognized. This has led to a large number of publications describing blood tests for AD, which have, for the most part, not been replicable. We have chosen to examine transcripts expressed by the cellular, leukocyte compartment of blood. We have used hypothesis-based cDNA arrays and quantitative PCR to quantify the expression of selected sets of genes followed by multivariate analyses in multiple independent samples...
June 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28716257/associations-between-white-matter-hyperintensities-and-cognitive-decline-over-three-years-in-non-dementia-older-adults-with-memory-complaints
#7
So Young Moon, Philipe de Souto Barreto, Marie Chupin, Jean François Mangin, Ali Bouyahia, Ludovic Fillon, Sandrine Andrieu, Bruno Vellas
We investigated whether the baseline level and overtime changes of white matter hyperintensities (WMH) would be associated with cognitive decline over three years in non-demented older adults with memory complaints. 109 participants with baseline magnetic resonance imaging (MRI) and follow-up cognitive assessments up to 3-year were included; among them, 82 also had a follow-up MRI assessment over three years. WMH volume was obtained by an automated segmentation algorithm. Baseline WMH volumes and change between baseline and follow-up WMH were related to cognitive scores over time using mixed-effect linear regressions...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28707482/peripheral-inflammation-apolipoprotein-e4-and-amyloid-%C3%AE-interact-to-induce-cognitive-and-cerebrovascular-dysfunction
#8
Felecia M Marottoli, Yuriko Katsumata, Kevin P Koster, Riya Thomas, David W Fardo, Leon M Tai
Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer's disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 ( APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28697560/relationship-between-body-mass-index-apoe4-status-and-pet-based-amyloid-and-neurodegeneration-markers-in-amyloid-positive-subjects-with-normal-cognition-or-mild-cognitive-impairment
#9
Janusch Blautzik, Sebastian Kotz, Matthias Brendel, Julia Sauerbeck, Franziska Vettermann, Yaroslav Winter, Peter Bartenstein, Kazunari Ishii, Axel Rominger
Body weight loss in late-life is known to occur at a very early stage of Alzheimer's disease (AD). Apolipoprotein E4 (ApoE4) represents a major genetic risk factor for AD and is linked to an increased cortical amyloid-β (Aβ) accumulation. Since the relationship between body weight, ApoE4, and AD pathology is poorly investigated, we aimed to evaluate whether ApoE4 allelic status modifies the association of body mass index (BMI) with markers of AD pathology. A total of 368 Aβ-positive cognitively healthy or mild cognitive impaired subjects had undergone [18F]-AV45-PET, [18F]-FDG-PET, and T1w-MRI examinations...
July 5, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28693655/longitudinal-assessment-of-self-and-informant-subjective-cognitive-complaints-in-a-sample-of-healthy-late-middle-aged-adults-enriched-with-a-family-history-of-alzheimer-s-disease
#10
Christopher R Nicholas, N Maritza Dowling, Annie M Racine, Lindsay R Clark, Sara E Berman, Rebecca L Koscik, Sanjay Asthana, Bruce Hermann, Mark A Sager, Sterling C Johnson
OBJECTIVES: The purpose of this study was to investigate the longitudinal trajectory of self- and informant-subjective cognitive complaints (SCC), and to determine if SCC predict longitudinal changes in objective measures (OM) of cognitive function. METHODS: The study included healthy and cognitively normal late middle-aged adults enriched with a family history of AD who were evaluated at up to three visits over a 4-year period. At each visit (Visit 1-3), self- and informant-SCC and OM were evaluated...
July 11, 2017: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/28688796/fatty-acid-based-lipidomics-and-membrane-remodeling-induced-by-apoe3-and-apoe4-in-human-neuroblastoma-cells
#11
Paraskevi Prasinou, Ioannis Dafnis, Giorgia Giacometti, Carla Ferreri, Angeliki Chroni, Chryssostomos Chatgilialoglu
Apolipoprotein E (apoE) is a major lipid carrier of the lipoprotein transport system that plays critical roles in various pathologies. Human apoE has three common isoforms, the apoE4 being associated with Alzheimer's disease. This is the first study in the literature investigating the effects of apoE (apoE3 and apoE4 isoforms) on membrane fatty acid profile in neuroblastoma SK-N-SH cells. Fatty acid analyses were carried out by gas chromatography of the corresponding methyl esters (FAME). We observed the occurrence of membrane fatty acid remodeling in the presence of each of the two apoE isoforms...
July 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28669331/patients-with-increased-non-ceruloplasmin-copper-appear-a-distinct-sub-group-of-alzheimer-s-disease-a-neuroimaging-study
#12
Rosanna Squitt, Ilaria Simonelli, Emanuele Cassetta, Domenico Lupoi, Mauro Rongioletti, Mariacarla Ventriglia, Mariacristina Siotto
BACKGROUND: Meta-analyses show that copper non-bound to ceruloplasmin (non-Cp Cu, also known as 'free' copper) in serum is higher in a percentage of Alzheimer's disease (AD) patients. Genetic heterogeneity in AD patients stratified on the basis of non-Cp Cu cut-off sustains the existence of a copper AD metabolic subtype. OBJECTIVE: In order to find evidence of the existence of a detectable metabolic subtype of AD associated to copper abnormalities, we explore the hypothesis of a neuroimaging pattern heterogeneity in an homogenous and well characterized AD population classified in two groups by the stratification of patients on the basis non-Cp Cu cut-off...
June 23, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28663518/amyloid-precursor-protein-and-endosomal-lysosomal-dysfunction-in-alzheimer-s-disease-inseparable-partners-in-a-multifactorial-disease
#13
REVIEW
Ralph A Nixon
Abnormalities of the endosomal-lysosomal network (ELN) are a signature feature of Alzheimer's disease (AD). These include the earliest known cytopathology that is specific to AD and that affects endosomes and induces the progressive failure of lysosomes, each of which are directly linked by distinct mechanisms to neurodegeneration. The origins of ELN dysfunction and β-amyloidogenesis closely overlap, which reflects their common genetic basis, the established early involvement of endosomes and lysosomes in amyloid precursor protein (APP) processing and clearance, and the pathologic effect of certain APP metabolites on ELN functions...
July 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28660014/apolipoprotein-e-a-multifunctional-protein-with-implications-in-various-pathologies-as-a-result-of-its-structural-features
#14
REVIEW
Irina Florina Tudorache, Violeta Georgeta Trusca, Anca Violeta Gafencu
Apolipoprotein E (apoE), a 34 kDa glycoprotein, mediates hepatic and extrahepatic uptake of plasma lipoproteins and cholesterol efflux from lipid-laden macrophages. In humans, three structural different apoE isoforms occur, with subsequent functional changes and pathological consequences. Here, we review data supporting the involvement of apoE structural domains and isoforms in normal and altered lipid metabolism, cardiovascular and neurodegenerative diseases, as well as stress-related pathological states...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28639714/plasma-cytokine-il-6-levels-and-subjective-cognitive-decline-preliminary-findings
#15
Andrew P Keegan, Daniel Paris, Cheryl A Luis, Laila Abdullah, Ghania Ait-Ghezala, David Beaulieu-Abdelahad, Makenzie Pryor, Jillian Chaykin, Gogce Crynen, Fiona Crawford, Michael Mullan
OBJECTIVE: Detection of Alzheimer's disease (AD) prior to clinical inception will be paramount for introducing disease modifying treatments. We have begun collecting baseline characteristics of a community cohort for longitudinal assessment and testing of antecedent blood-based biomarkers. We describe the baseline visit from the first 131 subjects in relationship to a commonly described cytokine, interleukin 6 (IL-6). METHODS: Subjects from the community presented for a free memory screening with varying degrees of memory concern...
June 22, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28634550/sortilin-related-receptor-expression-in-human-neural-stem-cells-derived-from-alzheimer-s-disease-patients-carrying-the-apoe-epsilon-4-allele
#16
Alen Zollo, Zoe Allen, Helle F Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten J Maier, Carmela Matrone
Alzheimer's disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28626809/epidermal-growth-factor-prevents-apoe4-induced-cognitive-and-cerebrovascular-deficits-in-female-mice
#17
Riya Thomas, Alan W J Morris, Leon M Tai
Cerebrovascular dysfunction is re-emerging as a major component of aging, and may contribute to the risk of developing Alzheimer's disease (AD). Two important risk factors for cerebrovascular dysfunction are APOE and female sex, which are primarily researched in the context of high amyloid-β (Aβ) levels as found in AD. However, APOE4 and sex modulate Aβ-independent pathways that may induce cerebrovascular dysfunction as a downstream consequence. Therefore, testing the activity of factors that target cerebrovascular dysfunction in Aβ-independent models that incorporate APOE4 and female sex is crucial...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28612048/obesity-accelerates-alzheimer-related-pathology-in-apoe4-but-not-apoe3-mice
#18
V Alexandra Moser, Christian J Pike
Alzheimer's disease (AD) risk is modified by both genetic and environmental risk factors, which are believed to interact to cooperatively modify pathogenesis. Although numerous genetic and environmental risk factors for AD have been identified, relatively little is known about potential gene-environment interactions in regulating disease risk. The strongest genetic risk factor for late-onset AD is the ε4 allele of apolipoprotein E (APOE4). An important modifiable risk factor for AD is obesity, which has been shown to increase AD risk in humans and accelerate development of AD-related pathology in rodent models...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28604016/triglycerides-are-negatively-correlated-with-cognitive-function-in-nondemented-aging-adults
#19
Vishnu Parthasarathy, Darvis T Frazier, Brianne M Bettcher, Laura Jastrzab, Linda Chao, Bruce Reed, Dan Mungas, Michael Weiner, Charles DeCarli, Helena Chui, Joel H Kramer
OBJECTIVE: Vascular risk factors like hyperlipidemia may adversely affect brain function. We hypothesized that increased serum triglycerides are associated with decreased executive function and memory in nondemented elderly subjects. We also researched possible vascular mediators and white matter microstructure as assessed with diffusion tensor imaging (DTI). DESIGN/METHOD: Participants were 251 nondemented elderly adults (54% male) with a mean age of 78 (SD = 6...
June 12, 2017: Neuropsychology
https://www.readbyqxmd.com/read/28597004/increased-binding-of-apolipoproteins-a-i-and-e4-to-triglyceride-rich-lipoproteins-is-linked-to-induction-of-hypertriglyceridemia
#20
Irina N Gorshkova, David Atkinson
Hypertriglyceridemia (HTG) is an independent factor of atherosclerotic cardiovascular disease and a hallmark of many metabolic disorders. However, the molecular etiology of HTG is still largely unknown. In mice, severe HTG may be induced by expression of specific mutants of apolipoprotein (apo) A-I or wild type (WT) apoE4. Expression of a certain apoE4 mutant results in mild HTG, while expression of another apoE4 mutant or WT apoA-I results in normal plasma triglyceride (TG) levels. Biophysical studies of the apoA-I and apoE4 forms associated with HTG help better understand the molecular mechanisms of induction of HTG by these proteins...
2017: JSM Atheroscler
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