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Alzheimer, amyloid beta, apolipoprotein

Cheng-Ta Chou, Yi-Chu Liao, Wei-Ju Lee, Shuu-Jiun Wang, Jong-Ling Fuh
BACKGROUND: The sortilin-related receptor 1 (SORL1) gene, regulating the trafficking and recycling of amyloid precursor protein, has been related to Alzheimer's disease (AD) and mild cognitive impairment (MCI). The aim of the present study was to investigate the relationship between SORL1 polymorphisms, plasma concentrations of amyloid-beta (Aβ) isoforms, and AD and MCI susceptibility for a Han Chinese population in Taiwan. METHODS: Eight single-nucleotide polymorphisms (SNPs) in SORL1 and the apolipoprotein E gene (APOE) ε4 alleles were genotyped in 798 patients with AD, 157 patients with MCI, and 401 control subjects...
December 30, 2016: Alzheimer's Research & Therapy
Zeenat Mirza, Mohd Amin Beg
Alzheimer's disease (AD) pathogenesis is primarily hallmarked by the production and accumulation of amyloid beta (Aβ) peptide. Along with the understanding of the neurodegenerative disease progression and its pathophysiological mechanisms, development of anti-Aβ targeted effective therapeutics is essential for AD management. Numerous therapeutic approaches targeting the production, toxicity and removal of Aβ are being attempted worldwide. Prime need is to design inhibitors which can slow down the Aβ aggregation process in a physiological environment...
November 14, 2016: Current Alzheimer Research
Alaina T Baker-Nigh, Kwasi G Mawuenyega, James G Bollinger, Vitaliy Ovod, Tom Kasten, Erin E Franklin, Fan Liao, Hong Jiang, David Holtzman, Nigel J Cairns, John C Morris, Randall J Bateman
The risk of Alzheimer's disease (AD) is highly dependent on apolipoprotein-E (apoE) genotype. The reasons for apoE isoform-selective risk are uncertain; however, both the amounts and structure of human apoE isoforms have been hypothesized to lead to amyloidosis increasing the risk for AD. To address the hypothesis that amounts of apoE isoforms are different in the human CNS, we developed a novel isoform-specific method to accurately quantify apoE isoforms in clinically relevant samples. The method utilizes an antibody-free enrichment step and isotope-labeled physiologically relevant lipoprotein particle standards produced by immortalized astrocytes...
December 30, 2016: Journal of Biological Chemistry
J M G van Bergen, X Li, J Hua, S J Schreiner, S C Steininger, F C Quevenco, M Wyss, A F Gietl, V Treyer, S E Leh, F Buck, R M Nitsch, K P Pruessmann, P C M van Zijl, C Hock, P G Unschuld
Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aβ) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aβ-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aβ-plaque-load was observable both for cortical and subcortical brain-regions...
October 17, 2016: Scientific Reports
Qingxiang Song, Huahua Song, Jianrong Xu, Jialin Huang, Meng Hu, Xiao Gu, Juan Chen, Gang Zheng, Hongzhuan Chen, Xiaoling Gao
Amyloid beta (Aβ) and its aggregation forms in the brain have been suggested as key targets for the therapy of Alzheimer's disease (AD). Therefore, the development of nanocarriers that possess both blood-brain barrier permeability and Aβ-targeting ability is of great importance for the intervention of AD. Here we constructed a biomimetic nanocarrier named apolipoprotein E (ApoE)-reconstituted high density lipoprotein nanocarrier (ANC) from recombinant ApoE and synthetic lipids to achieve the above goals. α-Mangostin (α-M), a polyphenolic agent that can inhibit the formation of Aβ oligomers and fibrils and accelerate Aβ cellular degradation, was used as the model drug...
November 7, 2016: Molecular Pharmaceutics
Camilla Steen Jensen, Erik Portelius, Volkert Siersma, Peter Høgh, Lene Wermuth, Kaj Blennow, Henrik Zetterberg, Gunhild Waldemar, Steen Gregers Hasselbalch, Anja Hviid Simonsen
BACKGROUND: Physical exercise may have some effect on cognition in patients with Alzheimer disease (AD). However, the underlying biochemical effects are unclear. Animal studies have shown that amyloid beta (Aβ), one of the pathological hallmarks of AD, can be altered with high levels of physical activity. AIM: The objective of this study was to elucidate the effect of 16 weeks of moderate- to high-intensity physical exercise on the biomarkers of AD, with special emphasis on the amyloidogenic pathway...
2016: Dementia and Geriatric Cognitive Disorders
A Manousopoulou, M Gatherer, C Smith, J A R Nicoll, C H Woelk, M Johnson, R Kalaria, J Attems, S D Garbis, R O Carare
AIMS: Amyloid beta (Aβ) accumulation in the walls of leptomeningeal arteries as cerebral amyloid angiopathy (CAA) is a major feature of Alzheimer's disease. In this study, we used global quantitative proteomic analysis to examine the hypothesis that the leptomeningeal arteries derived from patients with CAA have a distinct endophenotypic profile compared to those from young and elderly controls. METHODS: Freshly dissected leptomeningeal arteries from the Newcastle Brain Tissue Resource and Edinburgh Sudden Death Brain Bank from seven elderly (82...
October 5, 2016: Neuropathology and Applied Neurobiology
Amy L Heffernan, Cameron Chidgey, Po Peng, Colin L Masters, Blaine R Roberts
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterised by amyloid beta (Aβ) plaques and tau neurofibrillary tangles in the brain. Human apolipoprotein E (ApoE) is a lipid transport protein coded by the polymorphic APOE gene, with three major alleles: ε2, ε3 and ε4. After age, the ε4 allele is the greatest risk factor for developing sporadic AD, conferring an increased risk of 3-4 and 8-12 times for one or two copies of the allele, respectively. This risk is reported to vary by demographic factors including sex, ethnicity and geography...
November 2016: Journal of Molecular Neuroscience: MN
Felix L Yeh, Yuanyuan Wang, Irene Tom, Lino C Gonzalez, Morgan Sheng
Genetic variants of TREM2, a protein expressed selectively by microglia in the brain, are associated with Alzheimer's disease (AD). Starting from an unbiased protein microarray screen, we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands of TREM2. Binding of these ligands by TREM2 was abolished or reduced by disease-associated mutations. Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells, whereas TREM2 disease variants were impaired in this activity...
July 20, 2016: Neuron
Ioannis Dafnis, Letta Argyri, Marina Sagnou, Athina Tzinia, Effie C Tsilibary, Efstratios Stratikos, Angeliki Chroni
The apolipoprotein (apo) E4 isoform is the strongest risk factor for late-onset Alzheimer's disease (AD). ApoE4 is more susceptible to proteolysis than apoE2 and apoE3 isoforms and carboxyl-terminal truncated apoE4 forms have been found in AD patients' brain. We have previously shown that a specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (Aβ42) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis...
2016: Scientific Reports
Yifei Zhang, Lee Simon-Vermot, Miguel Á Araque Caballero, Benno Gesierich, Alexander N W Taylor, Marco Duering, Martin Dichgans, Michael Ewers
Resting-state functional connectivity (FC) is altered in Alzheimer's disease (AD) but its predictive value for episodic memory impairment is debated. Here, we aimed to assess whether resting-state FC in core brain regions activated during memory-task functional magnetic resonance imaging is altered and predictive of memory performance in AD and amnestic mild cognitive impairment (aMCI). Twenty-three elderly cognitively healthy controls (HC), 76 aMCI subjects, and 19 AD dementia patients were included. We computed resting-state FC between 18 meta-analytically determined peak coordinates of brain activation during successful memory retrieval...
September 2016: Neurobiology of Aging
Adrian Ivanoiu, Jérémie Pariente, Kevin Booth, Kasia Lobello, Gerald Luscan, Lisa Hua, Prisca Lucas, Scot Styren, Lingfeng Yang, David Li, Ronald S Black, H Robert Brashear, Thomas McRae
BACKGROUND: Immunotherapy with monoclonal antibodies that target amyloid beta has been under investigation as a treatment for patients with Alzheimer's disease (AD). The 3000 and 3001 phase 3 clinical studies of intravenous bapineuzumab assessed safety and efficacy in patients with mild to moderate AD recruited in over 26 countries. This article describes the long-term safety and tolerability of bapineuzumab in the extension studies for these two protocols. METHODS: The long-term safety and tolerability of intravenous-administered bapineuzumab in patients with AD was evaluated in apolipoprotein E ε4 allele noncarriers (Study 3002, extension of Study 3000) and apolipoprotein E ε4 allele carriers (Study 3003, extension of Study 3001)...
June 23, 2016: Alzheimer's Research & Therapy
Tim Hofer, George Perry
There is strong literature support for brain metal dysregulation, oxidative stress and oxidative damage to neurons in Alzheimer's disease (AD); these processes begin early and continue throughout the disease. Here, we review current knowledge on metal dysregulation and nucleic acid oxidative damage in AD (we also include new data demonstrating increased RNA and DNA oxidative damage in hippocampus from individuals having suffered from degenerative (e.g. AD) and psychological diseases: 8-oxo-7,8-dihydroguanine (8-oxoGua) levels as determined by HPLC-EC-UV were particularly elevated in RNA and heterogeneously distributed among adjacent regions versus the control)...
December 2016: Journal of Trace Elements in Medicine and Biology
Kevin P Koster, Conor Smith, Ana C Valencia-Olvera, Gregory R J Thatcher, Leon M Tai, Mary Jo LaDu
Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by amyloid plaques, composed of amyloid-beta peptide (Aβ) and neurofibrillary tangles, composed of aberrantly phosphorylated tau. APOE4 is the greatest genetic risk factor for AD, increasing risk up to 12-fold with a double allele compared to APOE3. In contrast, APOE2 reduces AD risk ~2-fold per allele. Accumulating evidence demonstrates that apolipoprotein E4 (apoE4) plays a multifactorial role in AD pathogenesis, although the exact mechanisms remain unclear...
June 16, 2016: Current Topics in Medicinal Chemistry
Hua Lin, Wen Huang, Biao Ye, Xiaoting Zhou, Xuean Mo
OBJECTIVE: To explore the clinical phenotype and genotype in a Chinese family affected with early-onset familial Alzheimer's disease (EOFAD). METHODS: Potential mutation of beta-amyloid precursor protein (APP) gene, presenilin 1 (PSEN1) gene and apolipoprotein E (APOE) gene was detected with polymerase chain reaction (PCR) and direct sequencing. RESULTS: Homozygous APOE ε 2 allele and no gene mutation of APP gene were detected in the proband (III1)...
June 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Veer Bala Gupta, James D Doecke, Eugene Hone, Steve Pedrini, Simon M Laws, Madhav Thambisetty, Ashley I Bush, Christopher C Rowe, Victor L Villemagne, David Ames, Colin L Masters, Stuart Lance Macaulay, Alan Rembach, Stephanie R Rainey-Smith, Ralph N Martins
INTRODUCTION: For early detection of Alzheimer's disease (AD), the field needs biomarkers that can be used to detect disease status with high sensitivity and specificity. Apolipoprotein J (ApoJ, also known as clusterin) has long been associated with AD pathogenesis through various pathways. The aim of this study was to investigate the potential of plasma apoJ as a blood biomarker for AD. METHODS: Using the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, the present study assayed plasma apoJ levels over baseline and 18 months in 833 individuals...
2016: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Eloise H Kok, Toni T Karppinen, Teemu Luoto, Irina Alafuzoff, Pekka J Karhunen
BACKGROUND: Controversy surrounds the effect of alcohol consumption on the development of dementia and cognitive impairment. We investigated the association between consumption of different alcoholic beverages and β-amyloid (Aβ) aggregation in the brain, 1 of the neuropathological lesions of Alzheimer's disease. METHODS: In total, 125 males of the Helsinki Sudden Death autopsy Series were included with an age range at death 35 to 70 years. The consumption of alcohol, Aβ aggregation in the brain, and Apolipoprotein E (APOE) genotype were assessed...
July 2016: Alcoholism, Clinical and Experimental Research
Alison J Yarnall, Tammaryn Lashley, Helen Ling, Andrew J Lees, Shirley Y Coleman, Sean S O'Sullivan, Yaroslau Compta, Tamas Revesz, David J Burn
INTRODUCTION: Evidence from clinical and pathological studies suggests a role for both alpha-synuclein and amyloid-beta in the pathophysiology of dementia associated with PD. Recent work demonstrated improvement in memory and reduced amyloid-beta burden in transgenic murine Alzheimer's models given subcutaneous apomorphine. The aim of this work was to determine whether antemortem exposure to apomorphine was associated with lower levels of amyloid-beta in brain tissue in a clinicopathological study of PD...
May 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Angela J Hanson, William A Banks, Hector Hernandez Saucedo, Suzanne Craft
BACKGROUND: Glucose intolerance and apolipoprotein ε4 allele (E4+) are risk factors for Alzheimer's disease (AD). Insulin sensitizers show promise for treating AD, but are less effective in E4+ individuals. Little is known about how the APOE genotype influences glucose metabolism. METHODS: Cross-sectional analysis of 319 older adults who underwent oral glucose tolerance tests; a subset had insulin, amyloid beta (Aβ42), and Mini Mental Status Examination. Glucose and insulin patterns with respect to cognitive diagnosis, E4 status, and sex were examined with analysis of covariance and Pearson correlation...
January 2016: Dementia and Geriatric Cognitive Disorders Extra
Ricardo S Osorio, Emma L Ducca, Margaret E Wohlleber, Emily B Tanzi, Tyler Gumb, Akosua Twumasi, Samuel Tweardy, Clifton Lewis, Esther Fischer, Viachaslau Koushyk, Maria Cuartero-Toledo, Mohammed O Sheikh, Elizabeth Pirraglia, Henrik Zetterberg, Kaj Blennow, Shou-En Lu, Lisa Mosconi, Lidia Glodzik, Sonja Schuetz, Andrew W Varga, Indu Ayappa, David M Rapoport, Mony J de Leon
STUDY OBJECTIVES: To evaluate the role of orexin-A with respect to cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers, and explore its relationship to cognition and sleep characteristics in a group of cognitively normal elderly individuals. METHODS: Subjects were recruited from multiple community sources for National Institutes of Health supported studies on normal aging, sleep and CSF biomarkers. Sixty-three participants underwent home monitoring for sleep-disordered breathing, clinical, sleep and cognitive evaluations, as well as a lumbar puncture to obtain CSF...
June 1, 2016: Sleep
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