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https://www.readbyqxmd.com/read/29147949/physical-activity-across-adulthood-and-subjective-cognitive-function-in-older-men
#1
Elinor Fondell, Mary Kay Townsend, Leslie Diane Unger, Olivia Ifeoma Okereke, Francine Grodstein, Alberto Ascherio, Walter Churchill Willett
Low subjective cognitive function (SCF), which is associated with APOE4 genotype, adversely impacts quality of life and has predicted clinical dementia. We examined whether physical activity during early adulthood or mid-to-late life is associated with late-life SCF. We followed 28,481 US male health professionals aged 40-75 years who reported their physical activity in 1986 and biennially thereafter. SCF was reported in 2008 and 2012. The SCF score was averaged for the 2008 and 2012 assessments and categorized as "good", "moderate", and "poor"...
November 17, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/29133888/neuronal-hyperactivity-due-to-loss-of-inhibitory-tone-in-apoe4-mice-lacking-alzheimer-s-disease-like-pathology
#2
Tal Nuriel, Sergio L Angulo, Usman Khan, Archana Ashok, Qiuying Chen, Helen Y Figueroa, Sheina Emrani, Li Liu, Mathieu Herman, Geoffrey Barrett, Valerie Savage, Luna Buitrago, Efrain Cepeda-Prado, Christine Fung, Eliana Goldberg, Steven S Gross, S Abid Hussaini, Herman Moreno, Scott A Small, Karen E Duff
The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer's disease (AD). However, the reason APOE4 is associated with increased AD risk remains a source of debate. Neuronal hyperactivity is an early phenotype in both AD mouse models and in human AD, which may play a direct role in the pathogenesis of the disease. Here, we have identified an APOE4-associated hyperactivity phenotype in the brains of aged APOE mice using four complimentary techniques-fMRI, in vitro electrophysiology, in vivo electrophysiology, and metabolomics-with the most prominent hyperactivity occurring in the entorhinal cortex...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29128930/prognostic-value-of-amyloid-pet-scan-in-normal-pressure-hydrocephalus
#3
Hyemin Jang, Seong Beom Park, Yeshin Kim, Ko Woon Kim, Jung Il Lee, Sung Tae Kim, Kyung Han Lee, Eun-Suk Kang, Yeong Sim Choe, Sang Won Seo, Hee Jin Kim, Yeo Jin Kim, Cindy W Yoon, Duk L Na
Amyloid positron emission tomography ([18F] florbetaben (FBB) PET) can be used to determine concomitant Alzheimer's disease (AD) in idiopathic normal pressure hydrocephalus (iNPH) patients. FBB PET scans and the tap test were performed in 31 patients with clinically suspected iNPH, and amyloid positive (iNPH/FBB+) and negative (iNPH/FBB-) groups were compared with respect to clinical characteristics. We evaluated prognostic value of FBB PET scans by analyzing the response to the tap test using a linear mixed model...
November 11, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/29125327/obstructive-sleep-apnea-severity-affects-amyloid-burden-in-cognitively-normal-elderly-a-longitudinal-study
#4
Ram A Sharma, Andrew W Varga, Omonigho M Bubu, Elizabeth Pirraglia, Korey Kam, Ankit Parekh, Margaret Wohlleber, Margo D Miller, Andreia Andrade, Clifton Lewis, Samuel Tweardy, Maja Buj, Po L Yau, Reem Sadda, Lisa Mosconi, Yi Li, Tracy Butler, Lidia Glodzik, Els Fieremans, James S Babb, Kaj Blennow, Henrik Zetterberg, Shou E Lu, Sandra G Badia, Sergio Romero, Ivana Rosenzweig, Nadia Gosselin, Girardin Jean-Louis, David M Rapoport, Mony J de Leon, Indu Ayappa, Ricardo S Osorio
RATIONALE: Recent evidence suggests that Obstructive Sleep Apnea (OSA) may be a risk factor for developing Mild Cognitive Impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. OBJECTIVE: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. METHODS: Data was derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly...
November 10, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29110615/effects-of-molecular-hydrogen-assessed-by-an-animal-model-and-a-randomized-clinical-study-on-mild-cognitive-impairment
#5
Kiyomi Nishimaki, Takashi Asada, Ikuroh Ohsawa, Etsuko Nakajima, Chiaki Ikejima, Takashi Yokota, Naomi Kamimura, Shigeo Ohta
BACKGROUND: Oxidative stress is one of the causative factors in the pathogenesis of neurodegenerative diseases including mild cognitive impairment (MCI) and dementia. We previously reported that molecular hydrogen (H2) acts as a therapeutic and preventive antioxidant. OBJECTIVE: We assess the effects of drinking H2-water (water infused with H2) on oxidative stress model mice and subjects with MCI. METHODS: Transgenic mice expressing a dominant-negative form of aldehyde dehydrogenase 2 were used as a dementia model...
November 6, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/29103040/association-of-low-level-ozone-with-cognitive-decline-in-older-adults
#6
Ekaterina Galkina Cleary, Manuel Cifuentes, Georges Grinstein, Doug Brugge, Thomas B Shea
Increasing evidence points to an association of airborne pollutant exposure with respiratory, cardiovascular, and neurological pathology. We examined whether or not ground-level ozone or fine particulate matter ≤ 2.5 μm in diameter (PM2.5) was associated with accelerated cognitive decline. Using repeated measures mixed regression modeling, we analyzed cognitive performance of a geographically diverse sampling of individuals from the National Alzheimer's Coordinating Center between 2004-2008. Ambient air concentrations of ozone and PM2...
November 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29100334/paradoxical-effects-of-137-cs-irradiation-on-pharmacological-stimulation-of-reactive-oxygen-species-in-hippocampal-slices-from-apoe2-and-apoe4-mice
#7
Laura E Villasana, Tunde Akinyeke, Sydney Weber, Jacob Raber
In humans, apoE, which plays a role in repair, is expressed in three isoforms: E2, E3, and E4. E4 is a risk factor for age-related cognitive decline (ACD) and Alzheimer's disease (AD), particularly in women. In contrast, E2 is a protective factor for ACD and AD. E2 and E4 might also differ in their response to cranial (137)Cs irradiation, a form of radiation typically used in a clinical setting for the treatment of cancer. This might be mediated by reactive oxygen species (ROS) in an-apoE isoform-dependent fashion...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29062035/csf-tau-is-associated-with-impaired-cortical-plasticity-cognitive-decline-and-astrocyte-survival-only-in-apoe4-positive-alzheimer-s-disease
#8
Giacomo Koch, Francesco Di Lorenzo, Stefano Loizzo, Caterina Motta, Sara Travaglione, Monica Baiula, Roberto Rimondini, Viviana Ponzo, Sonia Bonnì, Sofia Toniolo, Fabrizio Sallustio, Marco Bozzali, Carlo Caltagirone, Gabriele Campana, Alessandro Martorana
In Alzheimer's disease (AD) patients, apopoliprotein (APOE) polymorphism is the main genetic factor associated with more aggressive clinical course. However, the interaction between cerebrospinal fluid (CSF) tau protein levels and APOE genotype has been scarcely investigated. A possible key mechanism invokes the dysfunction of synaptic plasticity. We investigated how CSF tau interacts with APOE genotype in AD patients. We firstly explored whether CSF tau levels and APOE genotype influence disease progression and long-term potentiation (LTP)-like cortical plasticity as measured by transcranial magnetic stimulation (TMS) in AD patients...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038051/integrated-approach-reveals-diet-apoe-genotype-and-sex-affect-immune-response-in-app-mice
#9
Kyong Nyon Nam, Cody M Wolfe, Nicholas F Fitz, Florent Letronne, Emilie L Castranio, Anais Mounier, Jonathan Schug, Iliya Lefterov, Radosveta Koldamova
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is influenced by genetic and environmental risk factors, such as inheritance of ε4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of high fat diet (HFD) on amyloid pathology and expression profile in brains of AD model mice expressing human APOE isoforms (APP/E3 and APP/E4 mice). APP/E3 and APP/E4 mice were fed HFD or Normal diet for 3months. We found that HFD significantly increased amyloid plaques in male and female APP/E4, but not in APP/E3 mice...
October 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29034886/generation-and-characterization-of-human-induced-pluripotent-stem-cell-hipsc-lines-from-an-alzheimer-s-disease-asui001-a-and-non-demented-control-asui002-a-patient-homozygous-for-the-apolipoprotein-e4-apoe4-risk-variant
#10
Nicholas Brookhouser, Ping Zhang, Richard Caselli, Jean J Kim, David A Brafman
Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi001-A] and a non-demented control (NDC) patient [ASUi002-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and demonstrated the ability to differentiate into cells representative of the three germ layers...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29034839/pharmacogenetics-of-angiotensin-converting-enzyme-inhibitors-in-patients-with-alzheimer-s-disease-dementia
#11
Fabricio Ferreira de Oliveira, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci
BACKGROUND: While the angiotensin-converting enzyme degrades amyloid-β, angiotensin-converting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer's disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification...
October 16, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/29016679/perimenopause-and-emergence-of-an-alzheimer-s-bioenergetic-phenotype-in-brain-and-periphery
#12
Lisa Mosconi, Valentina Berti, Crystal Guyara-Quinn, Pauline McHugh, Gabriella Petrongolo, Ricardo S Osorio, Christopher Connaughty, Alberto Pupi, Shankar Vallabhajosula, Richard S Isaacson, Mony J de Leon, Russell H Swerdlow, Roberta Diaz Brinton
After advanced age, female sex is the major risk factor for Alzheimer's disease (AD). The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc) falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter...
2017: PloS One
https://www.readbyqxmd.com/read/28994390/clearance-of-beta-amyloid-is-facilitated-by-apolipoprotein-e-and-circulating-high-density-lipoproteins-in-bioengineered-human-vessels
#13
Jerome Robert, Emily B Button, Brian Yuen, Megan Gilmour, Kevin Kang, Arvin Bahrabadi, Sophie Stukas, Wenchen Zhao, Iva Kulic, Cheryl L Wellington
Amyloid plaques, consisting of deposited beta-amyloid (Aβ), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Aβ is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels...
October 10, 2017: ELife
https://www.readbyqxmd.com/read/28984314/alzheimer-disease-apoe4-implicated-in-tau-mediated-neurodegeneration
#14
Heather Wood
No abstract text is available yet for this article.
October 6, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28975146/effect-of-apolipoprotein-e-phenotype-on-the-association-of-plasma-amyloid%C3%A2-%C3%AE-and-amyloid-positron-emission-tomography-imaging-in-japan
#15
Amane Tateno, Takeshi Sakayori, Woo Chan Kim, Michihiko Koeda, Shinichiro Kumita, Hidenori Suzuki, Yoshiro Okubo
INTRODUCTION: The plasma concentration of beta-amyloid (Aβ) has been considered another biomarker of Alzheimer's disease and was reportedly associated with cortical Aβ accumulation. METHODS: We analyzed 28 subjects with apolipoprotein E4 (ApoE4; E4 group) and 89 subjects without ApoE4 (non-E4 group) to determine the association between cortical Aβ accumulation by standard uptake value ratio with [(18)F]florbetapir positron emission tomography and plasma Aβ1-40 and Aβ1-42...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28968233/peripheral-versus-central-index-of%C3%A2-metabolic-dysfunction-and-associations-with-clinical-and-pathological-outcomes-in%C3%A2-alzheimer-s-disease
#16
Kelsey E McLimans, Joseph L Webb, Vellareddy Anantharam, Anumantha Kanthasamy, Auriel A Willette
BACKGROUND/OBJECTIVE: Insulin-like growth factor binding protein 2 (IGFBP-2) regulates blood glucose levels, facilitates hippocampal synaptic plasticity and may have a predictive value for Alzheimer's disease (AD) diagnosis. METHODS: IGFBP-2 levels were studied in plasma in 566 subjects and in cerebrospinal fluid (CSF) in 245 subjects across the AD spectrum from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Variants in the IGFBP-2 gene were examined. Linear mixed modeling in SPSS tested main effects of IGFBP-2 and interactions with APOE4 on neurocognitive indices and biomarkers...
September 29, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28965825/the-glia-neuron-lactate-shuttle-and-elevated-ros-promote-lipid-synthesis-in-neurons-and-lipid-droplet-accumulation-in-glia-via-apoe-d
#17
Lucy Liu, Kevin R MacKenzie, Nagireddy Putluri, Mirjana Maletić-Savatić, Hugo J Bellen
Elevated reactive oxygen species (ROS) induce the formation of lipids in neurons that are transferred to glia, where they form lipid droplets (LDs). We show that glial and neuronal monocarboxylate transporters (MCTs), fatty acid transport proteins (FATPs), and apolipoproteins are critical for glial LD formation. MCTs enable glia to secrete and neurons to absorb lactate, which is converted to pyruvate and acetyl-CoA in neurons. Lactate metabolites provide a substrate for synthesis of fatty acids, which are processed and transferred to glia by FATP and apolipoproteins...
November 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28959956/apoe4-markedly-exacerbates-tau-mediated-neurodegeneration-in-a-mouse-model-of-tauopathy
#18
Yang Shi, Kaoru Yamada, Shane Antony Liddelow, Scott T Smith, Lingzhi Zhao, Wenjie Luo, Richard M Tsai, Salvatore Spina, Lea T Grinberg, Julio C Rojas, Gilbert Gallardo, Kairuo Wang, Joseph Roh, Grace Robinson, Mary Beth Finn, Hong Jiang, Patrick M Sullivan, Caroline Baufeld, Michael W Wood, Courtney Sutphen, Lena McCue, Chengjie Xiong, Jorge L Del-Aguila, John C Morris, Carlos Cruchaga, Anne M Fagan, Bruce L Miller, Adam L Boxer, William W Seeley, Oleg Butovsky, Ben A Barres, Steven M Paul, David M Holtzman
APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-β pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice...
September 28, 2017: Nature
https://www.readbyqxmd.com/read/28957663/apolipoprotein-e4-impairs-neuronal-insulin-signaling-by-trapping-insulin-receptor-in-the-endosomes
#19
Na Zhao, Chia-Chen Liu, Alexandra J Van Ingelgom, Yuka A Martens, Cynthia Linares, Joshua A Knight, Meghan M Painter, Patrick M Sullivan, Guojun Bu
Diabetes and impaired brain insulin signaling are linked to the pathogenesis of Alzheimer's disease (AD). The association between diabetes and AD-associated amyloid pathology is stronger among carriers of the apolipoprotein E (APOE) ε4 gene allele, the strongest genetic risk factor for late-onset AD. Here we report that apoE4 impairs neuronal insulin signaling in human apoE-targeted replacement (TR) mice in an age-dependent manner. High-fat diet (HFD) accelerates these effects in apoE4-TR mice at middle age...
September 27, 2017: Neuron
https://www.readbyqxmd.com/read/28945989/apolipoprotein-e4-inhibits-autophagy-gene-products-through-direct-specific-binding-to-clear-motifs
#20
Paul A Parcon, Meenakshisundaram Balasubramaniam, Srinivas Ayyadevara, Richard A Jones, Ling Liu, Robert J Shmookler Reis, Steven W Barger, Robert E Mrak, W Sue T Griffin
INTRODUCTION: Alzheimer apolipoprotein E (APOE) ɛ4/ɛ4 carriers have earlier disease onset and more protein aggregates than patients with other APOE genotypes. Autophagy opposes aggregation, and important autophagy genes are coordinately regulated by transcription factor EB (TFEB) binding to "coordinated lysosomal expression and regulation" (CLEAR) DNA motifs. METHODS: Autophagic gene expression was assessed in brains of controls and Alzheimer's disease (AD) patients parsed by APOE genotype and in a glioblastoma cell line expressing either apoE3 or apoE4...
September 22, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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