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https://www.readbyqxmd.com/read/28542068/reduced-cortical-excitatory-synapse-number-in-apoe4-mice-is-associated-with-increased-calcineurin-activity
#1
Aidan L Neustadtl, Charisse N Winston, Maia Parsadanian, Bevan S Main, Sonia Villapol, Mark P Burns
Synaptic loss is a symptom of Alzheimer's disease (AD) that is associated with the onset of cognitive decline and the loss of executive function. The strongest genetic risk factor for AD is the APOE4 allele, which results in both a greater risk of developing AD as well as an earlier age of onset of AD. Dendritic spines, the anatomical substrate of the excitatory synapse, are reduced in the cortex of humanized APOE4 mice but the reason for this synaptic decline is unknown. Calcineurin, a calcium/calmodulin dependent phosphatase, is a mediator of dendritic spine retraction...
May 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28533891/nuclear-uptake-of-an-amino-terminal-fragment-of-apolipoprotein-e4-promotes-cell-death-and-localizes-within-microglia-of-the-alzheimer-s-disease-brain
#2
Julia E Love, Ryan J Day, Justin W Gause, Raquel J Brown, Xinzhu Pu, Dustin I Theis, Chad A Caraway, Wayne W Poon, Abir A Rahman, Brad E Morrison, Troy T Rohn
Although harboring the apolipoprotein E4 (APOE4) allele is a well known risk factor in Alzheimer's disease (AD), the mechanism by which it contributes to disease risk remains elusive. To investigate the role of proteolysis of apoE4 as a potential mechanism, we designed and characterized a site-directed cleavage antibody directed at position D151 of the mature form of apoE4 and E3. Characterization of this antibody indicated a high specificity for detecting synthesized recombinant proteins corresponding to the amino acid sequences 1-151 of apoE3 and E4 that would generate the 17 kDa (p17) fragment...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/28528321/omega-3-fatty-acids-lipids-and-apoe-lipidation-in-alzheimer-s-disease-a-rationale-for-multi-nutrient-dementia-prevention
#3
Marcus O Grimm, Daniel Michaelson, Tobias Hartmann
In the last decade it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins which cleave APP close to and in the lipid bilayer. Moreover, apolipoprotein E4 (apoE4) has been identified as the most prevalent genetic risk factor for AD...
May 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28527212/apolipoprotein-e4-gender-body-mass-index-inflammation-insulin-resistance-and-air-pollution-interactions-recipe-for-alzheimer-s-disease-development-in-mexico-city-young-females
#4
Lilian Calderón-Garcidueñas, Suzanne M de la Monte
Given the epidemiological trends of increasing Alzheimer's disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Mexico City children experienced pre- and postnatal high exposures to PM2.5, O3, combustion-derived iron-rich nanoparticles, metals, polycyclic aromatic hydrocarbons, and endotoxins...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28507298/protective-effects-of-apoe-e2-against-disease-progression-in-subcortical-vascular-mild-cognitive-impairment-patients-a-three-year-longitudinal-study
#5
Yeo Jin Kim, Sang Won Seo, Seong Beom Park, Jin Ju Yang, Jin San Lee, Juyoun Lee, Young Kyoung Jang, Sung Tae Kim, Kyung-Han Lee, Jong Min Lee, Jae-Hong Lee, Jae Seung Kim, Duk L Na, Hee Jin Kim
Although the association between apolipoprotein E (APOE) genotype and disease progression is well characterized in patients with Alzheimer's disease, such a relationship is unknown in patients with subcortical vascular cognitive impairment. We evaluated whether APOE genotype is associated with disease progression in subcortical vascular mild cognitive impairment (svMCI) patients. We prospectively recruited 72 svMCI patients (19 APOE4 carriers, 42 APOE3 homozygotes, and 11 APOE2 carriers). Patients were annually followed-up with brain MRI and neuropsychological tests for three years and underwent a second Pittsburgh compound B (PiB)-PET at a mean interval of 32...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505977/hippocampal-and-clinical-trajectories-of-mild-cognitive-impairment-with-suspected-non-alzheimer-s-disease-pathology
#6
Jun Ku Chung, Eric Plitman, Shinichiro Nakajima, Fernando Caravaggio, Yusuke Iwata, Philip Gerretsen, Julia Kim, Hiroyoshi Takeuchi, Shunichiro Shinagawa, Raihaan Patel, M Mallar Chakravarty, Ariel Graff-Guerrero
Suspected non-Alzheimer's disease pathophysiology (SNAP) characterizes individuals showing neurodegeneration (e.g., hypometabolism) without amyloid-β (Aβ). Findings from previous studies regarding clinical and structural trajectories of SNAP are inconsistent. Using data from the Alzheimer's Disease Neuroimaging Initiative, patients with amnestic mild cognitive impairment (MCI) were categorized into four groups: amyloid positive with hypometabolism (Aβ+ND+), amyloid only (Aβ+ND-), neither amyloid nor hypometabolism (Aβ-ND-), and SNAP (Aβ-ND+)...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28502803/gene-co-expression-networks-identify-trem2-and-tyrobp-as-major-hubs-in-human-apoe-expressing-mice-following-traumatic-brain-injury
#7
Emilie L Castranio, Anais Mounier, Cody M Wolfe, Kyong Nyon Nam, Nicholas F Fitz, Florent Letronne, Jonathan Schug, Radosveta Koldamova, Iliya Lefterov
Traumatic brain injury (TBI) is strongly linked to an increased risk of developing dementia, including chronic traumatic encephalopathy and possibly Alzheimer's disease (AD). APOEε4 allele of human Apolipoprotein E (APOE) gene is the major genetic risk factor for late onset AD and has been associated with chronic traumatic encephalopathy and unfavorable outcome following TBI. To determine if there is an APOE isoform-specific response to TBI we performed controlled cortical impact on 3-month-old mice expressing human APOE3 or APOE4 isoforms...
May 11, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28482102/apolipoprotein-e4-allele-and-gait-performance-in-mild-cognitive-impairment-results-from-the-gait-and-brain-study
#8
Ryota Sakurai, Manuel Montero-Odasso
Background: The apolipoprotein E polymorphism ε4 allele (ApoE4) and gait impairment are both known risk factors for developing cognitive decline and dementia. However, it is unclear the interrelationship between these factors, particularly among older adults with mild cognitive impairment (MCI) who are considered as prodromal for Alzheimer's disease. This study aimed to determine whether ApoE4 carrier individuals with MCI may experience greater impairment in gait performance. Methods: Fifty-six older adults with MCI from the "Gait and Brain Study" who were identified as either ApoE4 carriers (n = 20) or non-ApoE4 carriers (n = 36) with 1 year of follow-up were included...
May 6, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28480324/the-effect-of-statins-on-rate-of-cognitive-decline-in-mild-cognitive-impairment
#9
Kyle B Smith, Paul Kang, Marwan N Sabbagh
OBJECTIVE: This study's aims are to identify whether or not a relationship between statin use and rate of cognitive decline exists. BACKGROUND: The relationship between statins and MCI has been investigated in the past with the evidence showing mixed results. METHODS: 768 subjects were identified with MCI. Subjects were stratified into 6 possible groups according to ApoE4 status and statin use and assessed for decline in cognitive function...
June 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28461186/apoe-%C3%AE%C2%B54-allele-elevates-the-expressions-of-inflammatory-factors-and-promotes-alzheimer-s-disease-progression-a-comparative-study-based-on-han-and-she-populations-in-the-wenzhou-area
#10
Yin-Ying Fan, Qiao-Le Cai, Zhi-Yong Gao, Xue Lin, Qi Huang, Wei Tang, Jia-Hong Liu
OBJECTIVE: This study aimed to investigate the impact of apolipoprotein E 4 (APOE4) gene polymorphisms on the expressions of inflammatory factors and the progression of Alzheimer's disease (AD). METHODS: A total of 185 AD patients (the case group, 130 cases from the Han ethnic group and 55 cases from the She ethnic group) and 190 healthy individuals (the control group, 130 cases from the Han ethnic group and 60 cases from the She ethnic group) were recruited for our study...
April 29, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28453482/higher-peripheral-trem2-mrna-levels-relate-to-cognitive-deficits-and-hippocampal-atrophy-in-alzheimer-s-disease-and-amnestic-mild-cognitive-impairment
#11
Yi Jayne Tan, Adeline S L Ng, Ashwati Vipin, Joseph K W Lim, Russell J Chander, Fang Ji, Yingwei Qiu, Simon K S Ting, Shahul Hameed, Tih-Shih Lee, Li Zeng, Nagaendran Kandiah, Juan Zhou
BACKGROUND: Variants in triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased Alzheimer's disease (AD) risk. Recent studies have reported inconsistent peripheral TREM2 mRNA expression levels and relationship with cognitive scores in AD and mild cognitive impairment (MCI). Additionally, no study has examined the association of peripheral TREM2 levels with neuroimaging measures in AD and MCI. OBJECTIVE: To determine peripheral TREM2 mRNA levels in AD, amnestic MCI (aMCI) and healthy controls, and the association with cognitive performance and brain structural changes...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28444230/apoe-%C3%AE%C2%B54-%C3%AE%C2%B54-diminishes-neurotrophic-function-of-human-ipsc-derived-astrocytes
#12
Jing Zhao, Mary D Davis, Yuka Atagi, Mitsuru Shinohara, Neill R Graff-Radford, Steven G Younkin, Zbigniew K Wszolek, Takahisa Kanekiyo, Guojun Bu
The ε4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong genetic risk factor for aging-related cognitive decline as well as late-onset Alzheimer's disease (AD) compared to the common ε3 allele. In the central nervous system, apoE is produced primarily by astrocytes and functions in transporting lipids including cholesterol to support neuronal homeostasis and synaptic integrity. Although mouse models and corresponding primary cells have provided valuable tools for studying apoE isoform-dependent functions, recent studies have shown that human astrocytes have distinct gene expression profile compare with rodent astrocytes...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28435985/elucidating-the-a%C3%AE-42-anti-aggregation-mechanism-of-action-of-tramiprosate-in-alzheimer-s-disease-integrating-molecular-analytical-methods-pharmacokinetic-and-clinical-data
#13
Petr Kocis, Martin Tolar, Jeremy Yu, William Sinko, Soumya Ray, Kaj Blennow, Howard Fillit, John A Hey
BACKGROUND: Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease...
April 24, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28434655/apolipoprotein-e-receptors-and-modulation-of-alzheimer-s-disease
#14
REVIEW
Na Zhao, Chia-Chen Liu, Wenhui Qiao, Guojun Bu
Apolipoprotein E (apoE) is a lipid carrier in both the peripheral and the central nervous systems. Lipid-loaded apoE lipoprotein particles bind to several cell surface receptors to support membrane homeostasis and injury repair in the brain. Considering prevalence and relative risk magnitude, the ε4 allele of the APOE gene is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). ApoE4 contributes to AD pathogenesis by modulating multiple pathways, including but not limited to the metabolism, aggregation, and toxicity of amyloid-β peptide, tauopathy, synaptic plasticity, lipid transport, glucose metabolism, mitochondrial function, vascular integrity, and neuroinflammation...
March 14, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28413778/family-history-and-apoe4-risk-for-alzheimer-s-disease-impact-the-neural-correlates-of-episodic-memory-by-early-midlife
#15
M N Rajah, L M K Wallace, E Ankudowich, E H Yu, A Swierkot, R Patel, M M Chakravarty, D Naumova, J Pruessner, R Joober, S Gauthier, S Pasvanis
Episodic memory impairment is a consistent, pronounced deficit in pre-clinical stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for AD exhibit altered brain function several decades prior to the onset of AD-related symptoms. In the current event-related fMRI study of spatial context memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a family history of late onset AD (MA+ FH), or a combined + FH and apolipoprotein E ε4 allele risk factors for AD (MA+ FH + APOE4), will exhibit differences in encoding and retrieval-related brain activity, compared to - FH - APOE4 MA controls...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28399184/genetic-factors-influencing-frontostriatal-dysfunction-and-the-development-of-dementia-in-parkinson-s-disease
#16
Ismael Huertas, Silvia Jesús, Francisco Javier García-Gómez, José Antonio Lojo, Inmaculada Bernal-Bernal, Marta Bonilla-Toribio, Juan Francisco Martín-Rodriguez, David García-Solís, Pilar Gómez-Garre, Pablo Mir
The dual syndrome hypothesis for cognitive impairment in Parkinson's disease (PD) establishes a dichotomy between a frontrostriatal dopamine-mediated syndrome, which leads to executive deficits, and a posterior cortical syndrome, which leads to dementia. Certain genes have been linked to these syndromes although the exact contribution is still controversial. The study's objective was to investigate the role of APOE, MAPT, COMT, SNCA and GBA genes in the dual syndromes. We genotyped APOE (rs429358 and rs7412), MAPT (rs9468), COMT (rs4680) and SNCA (rs356219) risk polymorphisms and sequenced GBA in a cohort of 298 PD patients...
2017: PloS One
https://www.readbyqxmd.com/read/28389477/efad-transgenic-mice-as-a-human-apoe-relevant-preclinical-model-of-alzheimer-s-disease
#17
Leon M Tai, Deebika Balu, Evangelina Avila-Munoz, Laila Abdullah, Riya Thomas, Nicole Collins, Ana Carolina Valencia-Olvera, Mary Jo LaDu
Identified in 1993, APOE4 is the greatest genetic risk factor for sporadic Alzheimers disease (AD), increasing risk up to 12-fold compared to APOE3, with APOE2 decreasing AD risk. However, the functional effects of APOE4 on AD pathology remain unclear and, in some cases, controversial. In vivo progress to understand how the human (h)-APOE genotypes effect AD pathology has been limited by the lack of a tractable familial AD-transgenic (FAD-Tg) mouse model expressing h- rather than mouse (m)-APOE. The disparity between m- and h-apoE is relevant for virtually every AD-relevant pathway, including amyloid beta deposition and clearance, neuroinflammation, tau pathology, neural plasticity and cerebrovascular deficits...
April 7, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28383643/observational-cohort-study-examining-apolipoprotein-e-status-and-preoperative-neuropsychological-performance-as-predictors-of-post-operative-delirium-in-an-older-elective-arthroplasty-population
#18
Emma Louise Cunningham, Tim Mawhinney, David Beverland, Seamus O'Brien, Daniel F McAuley, Rebecca Cairns, Peter Passmore, Bernadette McGuinness
Introduction: delirium following surgery is common and is associated with negative outcomes. Preoperative cognitive impairment has been shown to be a risk factor for post-operative delirium. Often the cognitive tests used are cumbersome. This study tests the hypothesis that the quantification of brain vulnerability, using Apolipoprotein E (ApoE) status and neuropsychological tests, both traditional and more easily administered, can quantify the risk of post-operative delirium following elective primary arthroplasty surgery...
April 5, 2017: Age and Ageing
https://www.readbyqxmd.com/read/28381516/randomized-controlled-trials-in-mild-cognitive-impairment-sources-of-variability
#19
Ronald C Petersen, Ronald G Thomas, Paul S Aisen, Richard C Mohs, Maria C Carrillo, Marilyn S Albert
OBJECTIVE: To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI). METHODS: Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil...
May 2, 2017: Neurology
https://www.readbyqxmd.com/read/28372324/apolipoprotein-e-isoforms-differentially-regulate-alzheimer-s-disease-and-amyloid-%C3%AE-induced-inflammatory-response-in-vivo-and-in-vitro
#20
Evan Dorey, Michelle Bamji-Mirza, Dema Najem, Yan Li, Hong Liu, Debbie Callaghan, Douglas Walker, Lih-Fen Lue, Danica Stanimirovic, Wandong Zhang
Neuroinflammation plays a critical role in neuronal dysfunction and death of Alzheimer's disease (AD). ApoE4 is a major risk factor of AD, while ApoE2 is neuroprotective. Little is known about the roles of ApoE isoforms in the neuroinflammation seen in AD. Their roles and mechanisms in Aβ-induced/neuroinflammation were investigated in this study using in vivo and in vitro models. Rat astrocytes were treated with lipid-poor recombinant hApoE and/or Aβ42. Mouse astrocyte lines-expressing lipidated hApoE were treated with Aβ42 and/or vitamin D receptor (VDR) agonist, 1α,25-dihydroxyvitamin D3...
2017: Journal of Alzheimer's Disease: JAD
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