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https://www.readbyqxmd.com/read/28225543/cuba-s-aging-and-alzheimer-longitudinal-study
#1
Juan de Jesús Llibre-Rodríguez, Adolfo Valhuerdi-Cepero, Ana M López-Medina, Lisseth Noriega-Fernández, Rutbeskia Porto-Álvarez, Milagros A Guerra-Hernández, Rodolfo I Bosch-Bayard, Tania Zayas-Llerena, Elaine Hernandez-Ulloa, Ana L Rodríguez-Blanco, Enrique Salazar-Pérez, Juan C Llibre-Guerra, Jorge J Llibre-Guerra, Beatriz Marcheco-Teruel
Aging and Alzheimer is a prospective, longitudinal cohort study involving 2944 adults aged ≥65 years from selected areas in Cuba's Havana and Matanzas Provinces. This door-to-door study, which began in 2003, includes periodic assessments of the cohort based on an interview; physical exam; anthropometric measurements; and diagnosis of dementia and its subtypes, other mental disorders, and other chronic non-communicable diseases and their risk factors. Information was gathered on sociodemographic characteristics; disability, dependency and frailty; use of health services; and characteristics of care and caregiver burden...
January 2017: MEDICC Review
https://www.readbyqxmd.com/read/28222108/oxidative-stress-mediated-nf%C3%AE%C2%BAb-phosphorylation-upregulates-p62-sqstm1-and-promotes-retinal-pigmented-epithelial-cell-survival-through-increased-autophagy
#2
Chunjuan Song, Sayak K Mitter, Xiaoping Qi, Eleni Beli, Haripriya V Rao, Jindong Ding, Colin S Ip, Hongmei Gu, Debra Akin, William A Dunn, Catherine Bowes Rickman, Alfred S Lewin, Maria B Grant, Michael E Boulton
p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE) and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress...
2017: PloS One
https://www.readbyqxmd.com/read/28213052/n-3-fatty-acids-mediterranean-diet-and-cognitive-function-in-normal-aging-a-systematic-review
#3
REVIEW
Maria F Masana, Ai Koyanagi, Josep Maria Haro, Stefanos Tyrovolas
BACKGROUND: Intake of n-3 fatty acids and adherence to the Mediterranean diet (MedDiet) have been shown to slow the progression of age-related cognitive decline, but the results are mixed. We summarized and evaluated the effect of n-3 fatty acids and MedDiet on cognitive outcomes in a cognitively healthy aged population. METHODS: Relevant published studies from January 2000 to May 2015 were identified by searching three electronic databases: Pubmed, Web of Science/MEDLINE, and CINHAL...
February 14, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28212683/evidence-for-benefit-of-statins-to-modify-cognitive-decline-and-risk-in-alzheimer-s-disease
#4
Nophar Geifman, Roberta Diaz Brinton, Richard E Kennedy, Lon S Schneider, Atul J Butte
BACKGROUND: Despite substantial research and development investment in Alzheimer's disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy...
February 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28209315/impact-of-apoe-genotypes-variations-on-toxoplasma-patients-with-dementia
#5
Raida S Yahya, Soha I Awad, Hatim A El-Baz, Niveen Saudy, Osama A Abdelsalam, Mohamed S Shehab Al-Din
BACKGROUND: Toxoplasma deprives host neuron cells from cholesterol and leads to its ability to potentiate dementia. ApoE intermediates neuronal transmission of cholesterol, which is a key constituent for axonal development, redesigning occasions that are important for education and synaptic arrangement, development of memory and repair of neuron. The aim of this work is to investigate the effect of ApoE genotypes on dementia associated with neurodegeneration in latent Toxoplasma gondii in elderly population...
February 10, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28173832/gene-environment-interaction-between-lead-and-apolipoprotein-e4-causes-cognitive-behavior-deficits-in-mice
#6
Anna K Engstrom, Jessica M Snyder, Nobuyo Maeda, Zhengui Xia
BACKGROUND: Alzheimer's disease (AD) is characterized by progressive cognitive decline and memory loss. Environmental factors and gene-environment interactions (GXE) may increase AD risk, accelerate cognitive decline, and impair learning and memory. However, there is currently little direct evidence supporting this hypothesis. METHODS: In this study, we assessed for a GXE between lead and ApoE4 on cognitive behavior using transgenic knock-in (KI) mice that express the human Apolipoprotein E4 allele (ApoE4-KI) or Apolipoprotein E3 allele (ApoE3-KI)...
February 7, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28164773/apolipoprotein-e-mediated-modulation-of-adam10-in-alzheimer-s-disease
#7
Ben Shackleton, Fiona Crawford, Corbin Bachmeier
BACKGROUND: The APOE4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). It has been associated with an accumulation of amyloid-β (Aβ) in the brain, which is produced through the sequential cleavage of the amyloid-β precursor protein (AβPP) by β- and γ-secretases. Alternatively, AβPP is also cleaved by α-secretases such as A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). OBJECTIVE: While several studies have investigated the impact of apoE on β- and γ-secretase, interactions between apoE and α-secretases have not been fully examined...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28160067/tau-aggregation-influences-cognition-and-hippocampal-atrophy-in-the-absence-of-beta-amyloid-a-clinico-imaging-pathological-study-of-primary-age-related-tauopathy-part
#8
Keith A Josephs, Melissa E Murray, Nirubol Tosakulwong, Jennifer L Whitwell, David S Knopman, Mary M Machulda, Stephen D Weigand, Bradley F Boeve, Kejal Kantarci, Leonard Petrucelli, Val J Lowe, Clifford R Jack, Ronald C Petersen, Joseph E Parisi, Dennis W Dickson
We investigate whether there is any association between the Braak neurofibrillary tangle (NFT) stage and clinical and MRI features in definite primary age-related tauopathy (PART). We analysed 52 cases with a Braak NFT tangle stage >0 and ≤IV, and a Thal phase of 0 (no beta-amyloid present). Twenty-nine (56%) were female. Median age at death was 88 years (IQR 82-92 years). Fifteen (29%) were TDP-positive (75% TDP stage I), 16 (31%) had argyrophilic grain disease and three (6%) had alpha-synuclein-positive Lewy bodies...
February 3, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28137305/peripheral-apoe-isoform-levels-in-cognitively-normal-apoe-%C3%AE%C2%B53-%C3%AE%C2%B54-individuals-are-associated-with-regional-gray-matter-volume-and-cerebral-glucose-metabolism
#9
Henrietta M Nielsen, Kewei Chen, Wendy Lee, Yinghua Chen, Robert J Bauer, Eric Reiman, Richard Caselli, Guojun Bu
BACKGROUND: Carriers of the APOE ε4 allele are at increased risk of developing Alzheimer's disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE ε4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated...
January 30, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28114437/association-of-docosahexaenoic-acid-supplementation-with-alzheimer-disease-stage-in-apolipoprotein-e-%C3%AE%C2%B54-carriers-a-review
#10
Hussein N Yassine, Meredith N Braskie, Wendy J Mack, Katherine J Castor, Alfred N Fonteh, Lon S Schneider, Michael G Harrington, Helena C Chui
Importance: The apolipoprotein E ε4 (APOE4) allele identifies a unique population that is at significant risk for developing Alzheimer disease (AD). Docosahexaenoic acid (DHA) is an essential ω-3 fatty acid that is critical to the formation of neuronal synapses and membrane fluidity. Observational studies have associated ω-3 intake, including DHA, with a reduced risk for incident AD. In contrast, randomized clinical trials of ω-3 fatty acids have yielded mixed and inconsistent results...
January 17, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28111074/apoe2-apoe3-and-apoe4-differentially-stimulate-app-transcription-and-a%C3%AE-secretion
#11
Yu-Wen Alvin Huang, Bo Zhou, Marius Wernig, Thomas C Südhof
Human apolipoprotein E (ApoE) apolipoprotein is primarily expressed in three isoforms (ApoE2, ApoE3, and ApoE4) that differ only by two residues. ApoE4 constitutes the most important genetic risk factor for Alzheimer's disease (AD), ApoE3 is neutral, and ApoE2 is protective. How ApoE isoforms influence AD pathogenesis, however, remains unclear. Using ES-cell-derived human neurons, we show that ApoE secreted by glia stimulates neuronal Aβ production with an ApoE4 > ApoE3 > ApoE2 potency rank order. We demonstrate that ApoE binding to ApoE receptors activates dual leucine-zipper kinase (DLK), a MAP-kinase kinase kinase that then activates MKK7 and ERK1/2 MAP kinases...
January 26, 2017: Cell
https://www.readbyqxmd.com/read/28106548/does-the-female-advantage-in-verbal-memory-contribute-to-underestimating-alzheimer-s-disease-pathology-in-women-versus-men
#12
Erin E Sundermann, Anat Biegon, Leah H Rubin, Richard B Lipton, Susan Landau, Pauline M Maki
There is a growing recognition of sex differences in Alzheimer's disease (AD). Females show an advantage over males on tests of verbal memory, which are used to diagnose AD and its precursor, amnestic mild cognitive impairment (aMCI). Women retain this advantage in aMCI despite reduced hippocampal volume and temporal lobe glucose metabolism. Here we examined whether this female advantage endures despite evidence of AD-specific pathology, cortical amyloid-β (Aβ) deposition measured with [18F]AV45 (florbetapir) positron emission tomography...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28096372/helical-structure-stability-and-dynamics-in-human-apolipoprotein-e3-and-e4-by-hydrogen-exchange-and-mass-spectrometry
#13
Palaniappan S Chetty, Leland Mayne, Sissel Lund-Katz, S Walter Englander, Michael C Phillips
Apolipoprotein E (apoE) plays a critical role in cholesterol transport in both peripheral circulation and brain. Human apoE is a polymorphic 299-residue protein in which the less common E4 isoform differs from the major E3 isoform only by a C112R substitution. ApoE4 interacts with lipoprotein particles and with the amyloid-β peptide, and it is associated with increased incidence of cardiovascular and Alzheimer's disease. To understand the structural basis for the differences between apoE3 and E4 functionality, we used hydrogen-deuterium exchange coupled with a fragment separation method and mass spectrometric analysis to compare their secondary structures at near amino acid resolution...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094792/identification-of-a-nuclear-respiratory-factor-1-recognition-motif-in-the-apolipoprotein-e-variant-apoe4-linked-to-alzheimer-s-disease
#14
Anne Urfer-Buchwalder, Roman Urfer
Alzheimer's disease affects tens of millions of people worldwide and its prevalence continues to rise. It is caused by a combination of a subject's heredity, environment, lifestyle, and medical condition. The most significant genetic risk factor for late onset Alzheimer's disease is a variant of the apolipoprotein E gene, APOE4. Here we show that the single nucleotide polymorphism rs429358 that defines APOE4 is located in a short sequence motif repeated several times within exon 4 of apolipoprotein E, reminiscent of the structure of transcriptional enhancers...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088659/altered-cerebral-insulin-response-in-transgenic-mice-expressing-the-epsilon-4-allele-of-the-human-apolipoprotein-e-gene
#15
Marie-Thérèse Traversy, Milène Vandal, Cyntia Tremblay, Marine Tournissac, Ariane Giguère-Rancourt, A David Bennett, Frédéric Calon
Apolipoprotein E epsilon-4 (APOEε4 or APOE4), an allelic variation of the APOE gene, not only increases the risk of developing the late-onset form of Alzheimer's disease (AD), but also influences the outcome of treatment. Indeed, data from clinical studies show that the beneficial effect of insulin on cognition is blunted in APOE4 carriers. To investigate how APOE impacts insulin response, we assessed the effects of an acute insulin injection in APOE3- and APOE4-targeted replacement mice that respectively express the human APOE3 or APOE4 isoform instead of the endogenous murine ApoE protein...
November 30, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28057414/apoe-apoe-receptors-and-the-synapse-in-alzheimer-s-disease
#16
REVIEW
Courtney Lane-Donovan, Joachim Herz
As the population ages, neurodegenerative diseases such as Alzheimer's disease (AD) are becoming a significant burden on patients, their families, and health-care systems. Neurodegenerative processes may start up to 15 years before outward signs and symptoms of AD, as evidenced by data from AD patients and mouse models. A major genetic risk factor for late-onset AD is the ɛ4 isoform of apolipoprotein E (ApoE4), which is present in almost 20% of the population. In this review we discuss the contribution of ApoE receptor signaling to the function of each component of the tripartite synapse - the axon terminal, the postsynaptic dendritic spine, and the astrocyte - and examine how these systems fail in the context of ApoE4 and AD...
January 2, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28035932/effect-of-vascular-risk-factors-on-the-progression-of-mild-alzheimer-s-disease-and-lewy-body-dementia
#17
Anne Katrine Bergland, Ingvild Dalen, Alf Inge Larsen, Dag Aarsland, Hogne Soennesyn
BACKGROUND: Vascular risk factors (VRF) are associated with an increased risk of neurodegenerative disease. OBJECTIVE: To examine the association between VRF and cognitive decline in patients with Alzheimer's disease (AD) and Lewy body dementia (LBD). METHODS: We included consecutive referrals with mild AD or LBD to dementia clinics in western Norway from 2005 to 2013. The Mini-Mental Status Exam (MMSE) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) were administered at baseline and then annually for up to five years...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035926/pleiotropic-effect-of-human-apoe4-on-cerebral-ceramide-and-saturated-fatty-acid-levels
#18
Sandra den Hoedt, Carola I F Janssen, Guiseppe Astarita, Daniele Piomelli, Frank P J Leijten, Simone M Crivelli, Adrie J M Verhoeven, Helga E de Vries, Jochen Walter, Pilar Martinez-Martinez, Eric J G Sijbrands, Amanda J Kiliaan, Monique T Mulder
BACKGROUND: Apolipoprotein E (ApoE) is known for its role in lipid trafficking and the ɛ4 allele is a risk factor for late onset Alzheimer's disease (AD). Recently, aberrant ceramide and fatty acid (FA) levels have been implicated in AD. OBJECTIVE: To determine the specific effects of human ApoE4 (hE4) on cerebral ceramide and FA content during chow or a high fat/high cholesterol (HFHC) diet. METHODS: Cerebral ceramide and FA profiles were determined by LC-MSMS in 15-month-old female wild-type (WT), ApoE-knockout (E0), and hE4-knockin mice fed chow or a HFHC diet for 3 months...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035917/apolipoprotein-e4-elicits-lysosomal-cathepsin-d-release-decreased-thioredoxin-1-levels-and-apoptosis
#19
Torbjörn Persson, Francesca Lattanzio, Javier Calvo-Garrido, Roberto Rimondini, Marta Rubio-Rodrigo, Erik Sundström, Silvia Maioli, Anna Sandebring-Matton, Ángel Cedazo-Mínguez
The major genetic risk factor for Alzheimer's disease (AD), apolipoprotein E4 (ApoE4), has been suggested to have detrimental effects on neurons, including direct toxicity via apoptosis. Thioredoxin-1 (Trx1) is an endogenous antioxidant protein important for redox regulation and participates in the regulation of apoptosis through the inhibition of apoptosis signal-regulating kinase-1 (Ask-1). In this study, we have investigated the effects of ApoE on Trx1 in the brain. Our results showed that the protein levels of Trx1 were reduced in the hippocampus of ApoE4 targeted replacement (TR) mice compared to ApoE3 TR mice...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28017255/cognitive-deficits-in-non-demented-diabetic-elderly-appear-independent-of-brain-amyloidosis
#20
Gloria C Chiang, Eileen Chang, Sneha Pandya, Amy Kuceyeski, James Hu, Richard Isaacson, Christine Ganzer, Aaron Schulman, Vivian Sobel, Shankar Vallabhajosula, Lisa Ravdin
BACKGROUND: To determine the effects of Type 2 diabetes (DM2) on levels of brain amyloidosis and cognition in a community-dwelling cohort of nondemented elderly individuals. METHODS: 33 subjects (16 DM2, 17 nondiabetic) were prospectively recruited. Subjects underwent a PET scan using the amyloid tracer, Pittsburgh Compound B, and a neuropsychological evaluation. Associations between DM2, brain amyloidosis, and cognition were assessed using multivariate regressions, adjusting for age and APOE4 status...
January 15, 2017: Journal of the Neurological Sciences
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