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https://www.readbyqxmd.com/read/28918391/genetic-polymorphisms-associated-with-the-risk-of-concussion-in-1056-college-athletes-a-multicentre-prospective-cohort-study
#1
Thomas Roland Terrell, Ruth Abramson, Jeffery T Barth, Ellen Bennett, Robert C Cantu, Richard Sloane, Daniel T Laskowitz, David M Erlanger, Douglas McKeag, Gregory Nichols, Verle Valentine, Leslie Galloway
BACKGROUND/AIM: To evaluate the association of genetic polymorphisms APOE, APOE G-219T promoter, microtubule associated protein(MAPT)/tau exon 6 Ser(53)Pro, MAPT/tau Hist(47)Tyr, IL-6572 G/C and IL-6R(Asp)358(Ala) with the risk of concussion in college athletes. METHODS: A 23-centre prospective cohort study of 1056 college athletes with genotyping was completed between August 2003 and December 2012. All athletes completed baseline medical and concussion questionnaires, and post-concussion data were collected for athletes with a documented concussion...
September 16, 2017: British Journal of Sports Medicine
https://www.readbyqxmd.com/read/28916386/molecular-mechanisms-of-the-r61t-mutation-in-apolipoprotein-e4-a-dynamic-rescue
#2
Benfeard Williams, Marino Convertino, Jhuma Das, Nikolay V Dokholyan
The apolipoprotein E4 (ApoE4) gene is the strongest genetic risk factor for Alzheimer's disease (AD). With respect to the other common isoforms of this protein (ApoE2 and ApoE3), ApoE4 is characterized by lower stability that underlies the formation of a stable interaction between the protein's N- and C-terminal domains. AD-related cellular dysfunctions have been linked to this ApoE4 misfolded state. In this regard, it has been reported that the mutation R61T is able to rescue the deleterious cellular effects of ApoE4 by preventing the formation of the misfolded intermediate state...
September 12, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28900205/apoe4-associated-phospholipid-dysregulation-contributes-to-development-of-tau-hyper-phosphorylation-after-traumatic-brain-injury
#3
Jiqing Cao, Farida El Gaamouch, James S Meabon, Kole D Meeker, Li Zhu, Margaret B Zhong, John Bendik, Gregory Elder, Ping Jing, Jiahong Xia, Wenjie Luo, David G Cook, Dongming Cai
The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer's Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP2) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP2 degrading enzyme, synaptojanin 1 (synj1). In contrast, hippocampal PIP2 levels in ApoE4 mice did not increase after blast TBI...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28879423/transcriptional-effects-of-apoe4-relevance-to-alzheimer-s-disease
#4
REVIEW
Veena Theendakara, Clare A Peters-Libeu, Dale E Bredesen, Rammohan V Rao
The major genetic risk factor for sporadic Alzheimer's disease (AD) is the lipid binding and transporting carrier protein apolipoprotein E, epsilon 4 allele (ApoE4). One of the unsolved mysteries of AD is how the presence of ApoE4 elicits this age-associated, currently incurable neurodegenerative disease. Recently, we showed that ApoE4 acts as a transcription factor and binds to the promoters of genes involved in a range of processes linked to aging and AD disease pathogenesis. These findings point to novel therapeutic strategies for AD and aging, resulting in an extension of human healthspan, the disease-free and functional period of life...
September 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28869468/association-of-gait-speed-psychomotor-speed-and-dementia
#5
Callixte Kuate-Tegueu, José-Alberto Avila-Funes, Nadine Simo, Mélanie Le Goff, Hélène Amiéva, Jean-François Dartigues, Maturin Tabue-Teguo
BACKGROUND: Gait speed (GS) and psychomotor speed (PS) could be considered as two different dimensions of age-related slowness and both measures are associated with higher risk of adverse health-related outcomes among elderly people. OBJECTIVE: To determine the association between GS, PS, and incident dementia among community-dwelling older adults. METHODS: Twelve-year longitudinal study of 1,265 participants in the Bordeaux Three-City Study, a French prospective to determine the risk of dementia and cognitive impairment attributable to cardiovascular risk factors...
August 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28861336/a-whole-brain-computational-modeling-approach-to-explain-the-alterations-in-resting-state-functional-connectivity-during-progression-of-alzheimer-s-disease
#6
Murat Demirtaş, Carles Falcon, Alan Tucholka, Juan Domingo Gispert, José Luis Molinuevo, Gustavo Deco
Alzheimer's disease (AD) is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC) of the subjects with preclinical Alzheimer's disease (PAD), mild cognitive impairment due to AD (MCI) and mild dementia due to Alzheimer's disease (AD), the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28855400/sex-differences-in-alzheimer-risk-brain-imaging-of-endocrine-vs-chronologic-aging
#7
Lisa Mosconi, Valentina Berti, Crystal Quinn, Pauline McHugh, Gabriella Petrongolo, Isabella Varsavsky, Ricardo S Osorio, Alberto Pupi, Shankar Vallabhajosula, Richard S Isaacson, Mony J de Leon, Roberta Diaz Brinton
OBJECTIVE: This observational multimodality brain imaging study investigates emergence of endophenotypes of late-onset Alzheimer disease (AD) risk during endocrine transition states in a cohort of clinically and cognitively normal women and age-matched men. METHODS: Forty-two 40- to 60-year-old cognitively normal women (15 asymptomatic perimenopausal by age [CNT], 13 perimenopausal [PERI], and 14 postmenopausal [MENO]) and 18 age- and education-matched men were examined...
August 30, 2017: Neurology
https://www.readbyqxmd.com/read/28808293/targeting-apolipoprotein-e-amyloid-%C3%AE-binding-by-peptoid-cpo_a%C3%AE-17-21%C3%A2-p-ameliorates-alzheimer-s-disease-related-pathology-and-cognitive-decline
#8
Shan Liu, Shinae Park, Grant Allington, Frances Prelli, Yanjie Sun, Mitchell Martá-Ariza, Henrieta Scholtzova, Goutam Biswas, Bernard Brown, Philip B Verghese, Pankaj D Mehta, Yong-Uk Kwon, Thomas Wisniewski
Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Studies have shown that apoE, apoE4 in particular, binds to amyloid-β (Aβ) peptides at residues 12-28 of Aβ and this binding modulates Aβ accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE/Aβ interaction with Aβ12-28 P reduced Aβ and tau-related pathology, leading to cognitive improvements in treated AD mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28802628/physical-activity-domains-and-cognitive-function-over-three-years-in-older-adults-with-subjective-memory-complaints-secondary-analysis-from-the-mapt-trial
#9
Philipe de Souto Barreto, Sandrine Andrieu, Yves Rolland, Bruno Vellas
OBJECTIVES: We aimed to examine the associations of physical activity (PA) domains (i.e., PA in leisure-time (LTPA), for housework (HPA), or for gardening (GPA)) with cognitive function in older adults with subjective memory complaints (no-dementia) and to investigate if those associations were dependent on the status of apolipoprotein E allele 4 (APOE4), omega-3 levels and mild cognitive impairment (MCI). DESIGN: Observational prospective secondary analysis using longitudinal data from a randomized controlled trial...
July 26, 2017: Journal of Science and Medicine in Sport
https://www.readbyqxmd.com/read/28800331/alzheimer-s-disease-biomarkers-interactively-influence-physical-activity-mobility-and-cognition-associations-in%C3%A2-a%C3%A2-non-demented-aging-population
#10
Sherilyn Thibeau, G Peggy McFall, Richard Camicioli, Roger A Dixon
BACKGROUND: Alzheimer's disease (AD) risk-reduction strategies (e.g., increasing physical activity, improving mobility) have garnered increasing attention in the literature. However, the effect of such modifiable factors on the preclinical trajectories of brain and cognitive health may be moderated by non-modifiable biomarkers associated with AD. OBJECTIVE: In a longitudinal sample of non-demented older adults, we examine the independent predictors everyday physical activity (EPA) and mobility on executive function (EF) performance and change...
August 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28775055/in-vivo-imaging-of-venous-side-cerebral-small-vessel-disease-in-older-adults-an-mri-method-at-7t
#11
C E Shaaban, H J Aizenstein, D R Jorgensen, R L MacCloud, N A Meckes, K I Erickson, N W Glynn, J Mettenburg, J Guralnik, A B Newman, T S Ibrahim, P J Laurienti, A N Vallejo, C Rosano
BACKGROUND AND PURPOSE: Traditional neuroimaging markers of small-vessel disease focus on late-stage changes. We aimed to adapt a method of venular assessment at 7T for use in older adults. We hypothesized that poorer venular morphologic characteristics would be related to other small-vessel disease neuroimaging markers and a higher prevalence of small-vessel disease-Alzheimer disease risk factors. MATERIALS AND METHODS: Venules were identified in periventricular ROIs on SWI and defined as tortuous or straight...
August 3, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28752509/the-association-of-apolipoprotein-e-allele-4-polymorphism-with-the-recovery-of-sleep-disturbance-after-mild-traumatic-brain-injury
#12
Hsun-Hua Lee, Chun-Ting Yeh, Ju-Chi Ou, Hon-Ping Ma, Kai-Yun Chen, Cheng-Fu Chang, Jing-Huei Lai, Kuo-Hsing Liao, Chien-Min Lin, Shu-Yu Lin, Dean Wu, Yao-Hsien Huang, Chaur-Jong Hu, Chien-Tai Hong
PURPOSE: Mild traumatic brain injury (mTBI) is a major public health concern. The apolipoprotein E (APOE) gene contains three polymorphisms, and the APOE4 polymorphism may affect several physiological states, such as the recovery from mTBI as well as sleep. This study aims to investigate the association between APOE4 with the recovery of sleep disturbance after mTBI. METHODS: From May 2012 to Aug 2015, 189 mTBI patients completed baseline (1st week post-mTBI) and follow-up (6th week post-mTBI) sleep assessments that involved using the Pittsburgh Sleep Quality Index (PSQI)...
March 15, 2017: Acta Neurologica Taiwanica
https://www.readbyqxmd.com/read/28750690/increased-a%C3%AE-42-%C3%AE-7-like-nicotinic-acetylcholine-receptor-complex-level-in-lymphocytes-is-associated-with-apolipoprotein-e4-driven-alzheimer-s-disease-pathogenesis
#13
Hoau-Yan Wang, Caryn Trocmé-Thibierge, Andres Stucky, Sanket M Shah, Jessica Kvasic, Amber Khan, Philippe Morain, Isabelle Guignot, Eva Bouguen, Karine Deschet, Maria Pueyo, Elisabeth Mocaer, Pierre-Jean Ousset, Bruno Vellas, Vera Kiyasova
BACKGROUND: The apolipoprotein E ε4 (APOE4) genotype is a prominent late-onset Alzheimer's disease (AD) risk factor. ApoE4 disrupts memory function in rodents and may contribute to both plaque and tangle formation. METHODS: Coimmunoprecipitation and Western blot detection were used to determine: 1) the effects of select fragments from the apoE low-density lipoprotein (LDL) binding domain and recombinant apoE subtypes on amyloid beta (Aβ)42-α7 nicotinic acetylcholine receptor (α7nAChR) interaction and tau phosphorylation in rodent brain synaptosomes; and 2) the level of Aβ42-α7nAChR complexes in matched controls and patients with mild cognitive impairment (MCI) and dementia due to AD with known APOE genotypes...
July 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28744113/apolipoprotein-%C3%AE%C2%B57-allele-in-memory-complaints-insights-through-protein-structure-prediction
#14
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
#15
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)...
October 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
#16
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...
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
#17
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)...
September 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
#18
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
#19
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
#20
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
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