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Alzheimer apoe

Gonzalo Sánchez-Benavides, Juan D Gispert, Karine Fauria, José Luis Molinuevo, Nina Gramunt
INTRODUCTION: Repetitive administration of neuropsychological tests can lead to performance improvement merely due to previous exposure. The magnitude of such practice effects (PEs) may be used as a marker of subtle cognitive impairment because they are diminished in healthy individuals subsequently developing Alzheimer's disease (AD). METHODS: To explore the relationship between sociodemographic factors, AD family history (FH), and APOE ε4 status, and the magnitude of PE, four subtests of the Wechsler Adult Intelligence Scale-IV were administered twice to 400 middle-aged healthy individuals, most of them first-degree descendants of AD patients...
2016: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Carlos Gueto-Tettay, Joshua Zuchniarz, Yeyson Fortich-Seca, Luis Roberto Gueto-Tettay, Juan Carlos Drosos-Ramirez
BACE1 is an aspartyl protease which is a therapeutic target for Alzheimer's disease (AD) because of its participation in the rate-limiting step in the production of Aβ-peptide, the accumulation of which produces senile plaques and, in turn, the neurodegenerative effects associated with AD. The active site of this protease is composed in part by two aspartic residues (Asp93 and Asp289). Additionally, the catalytic site has been found to be covered by an antiparallel hairpin loop called the flap. The dynamics of this flap are fundamental to the catalytic function of the enzyme...
October 7, 2016: Journal of Molecular Graphics & Modelling
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
Antti J Luikku, Anette Hall, Ossi Nerg, Anne M Koivisto, Mikko Hiltunen, Seppo Helisalmi, Sanna-Kaisa Herukka, Anna Sutela, Maria Kojoukhova, Jussi Mattila, Jyrki Lötjönen, Jaana Rummukainen, Irina Alafuzoff, Juha E Jääskeläinen, Anne M Remes, Hilkka Soininen, Ville Leinonen
OBJECTIVES: Optimal selection of idiopathic normal pressure hydrocephalus (iNPH) patients for shunt surgery is challenging. Disease State Index (DSI) is a statistical method that merges multimodal data to assist clinical decision-making. It has previously been shown to be useful in predicting progression in mild cognitive impairment and differentiating Alzheimer's disease (AD) and frontotemporal dementia. In this study, we use the DSI method to predict shunt surgery response for patients with iNPH...
October 14, 2016: Acta Neurochirurgica
Qing Ye, Fan Su, Hao Shu, Liang Gong, Chunming Xie, Zhijun Zhang, Feng Bai
Previous cross-sectional studies that investigated the effects of apolipoprotein E (ApoE) ε4 status on hippocampal networks have shown inconsistent results. Aging is a well-known risk factor for Alzheimer's disease (AD) and could strongly interact with ApoE-related vulnerabilities to affect AD risk. However, no longitudinal data have been published regarding the interaction of the ApoE genotype and aging on hippocampal networks. Fifty-one patients with amnestic-type mild cognitive impairment (aMCI) and 64 matched cognitively normal elderly subjects underwent resting-state fMRI scans and neuropsychological tests at baseline and at a 35-month follow-up...
October 12, 2016: Brain Imaging and Behavior
Philip S Insel, Sebastian Palmqvist, R Scott Mackin, Rachel L Nosheny, Oskar Hansson, Michael W Weiner, Niklas Mattsson
INTRODUCTION: Clinical trials in Alzheimer's disease are aimed at early stages of disease, including preclinical Alzheimer's disease. The high cost and time required to screen large numbers of participants for Aβ pathology impede the development of novel drugs. This study's objective was to evaluate the extent to which inexpensive and easily obtainable information can reduce the number of screen failures by increasing the proportion of Aβ+ participants identified for screening. METHODS: We used random forest models to evaluate the positive predictive value of demographics, APOE, and longitudinal cognitive rates in the prediction of amyloid pathology, measured by florbetapir PET or cerebrospinal fluid...
2016: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Keqiang Chen, Ruoxi Yuan, Shuo Geng, Yao Zhang, Taojing Ran, Elizabeth Kowalski, Jingze Liu, Liwu Li
The excessive accumulation of specific cellular proteins or autophagic vacuoles (AVs) within neurons is a pathologic hallmark of neurodegenerative diseases. Constitutive autophagy in neurons prevents abnormal intracellular protein aggregation and is critical for maintaining cell survival. Since our previous study showed that Toll-interacting protein (Tollip)-deficient macrophages had constitutive disruption of endosome-lysosome fusion, we hypothesize that Tollip deficiency may also promote neuron death via blockage of autophagy completion...
October 5, 2016: Brain, Behavior, and Immunity
Gennady V Roshchupkin, Hieab H Adams, Sven J van der Lee, Meike W Vernooij, Cornelia M van Duijn, Andre G Uitterlinden, Aad van der Lugt, Albert Hofman, Wiro J Niessen, Mohammad A Ikram
The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions...
September 4, 2016: Neurobiology of Aging
Feng Lin, Ping Ren, Raymond Y Lo, Benjamin P Chapman, Alanna Jacobs, Timothy M Baran, Anton P Porsteinsson, John J Foxe
Apolipoprotein E (APOE) ɛ4 carriers and patients with amnestic mild cognitive impairment (MCI) have high risk of developing Alzheimer's disease (AD). The Scaffolding Theory of Aging and Cognition proposes that recruitment of additional frontal brain regions can protect cognition against aging. This thesis has yet to be fully tested in older adults at high risk for AD. In the present study, 75 older participants (mean age: 74 years) were included. Applying a voxel-wise approach, fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional neuroimaging data were analyzed as a function of APOEɛ4 status (carrier versus noncarrier) and clinical status (healthy control [HC] versus MCI) using a 2×2 analysis of covariance (ANCOVA)...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Luís F J R Miranda, Karina B Gomes, Pedro A L Tito, Josianne N Silveira, Gerson A Pianetti, Ricardo M D Byrro, Patrícia R H Peles, Fernando H Pereira, Thiago R Santos, Arthur G Assini, Valéria V Ribeiro, Edgar N Moraes, Paulo Caramelli
The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and of APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Xiao Luo, Tiantian Qiu, Yunlu Jia, Peiyu Huang, Xiaojun Xu, Xinfeng Yu, Zhujing Shen, Yerfan Jiaerken, Xiaojun Guan, Jiong Zhou, Minming Zhang
Apolipoprotein E (APOE) ε4 allele is the best established genetic risk factor for sporadic Alzheimer's disease (AD). However, there is a need to understand the effects of this genotype on the brain by simultaneously assessing intrinsic brain network and cerebral spinal fluid (CSF) biomarkers changes in healthy older ε4 carriers. Thirteen cognitively intact, elderly APOE ε4 carriers and 22 ε3 homozygotes were included in the present study. Eigenvector centrality mapping (ECM) was used to identify brain network hub organization based on resting-state functional MRI (rsfMRI)...
October 6, 2016: Brain Imaging and Behavior
R J Kryscio, E L Abner, P T Nelson, D Bennett, J Schneider, L Yu, L S Hemmy, K O Lim, K Masaki, N Cairns, C Xiong, R Woltjer, H H Dodge, S Tyas, D W Fardo, W Lou, L Wan, F A Schmitt
BACKGROUND: Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. OBJECTIVE: To correlate measures of cerebral vascular pathology with cognitive trajectories. SETTING: Observational study. PARTICIPANTS: A cohort of 2,274 individuals who came to autopsy at a mean age of 89...
June 2016: Journal of Prevention of Alzheimer's Disease
Stefan J Kempf, Dirk Janik, Zarko Barjaktarovic, Ignacia Braga-Tanaka Iii, Satoshi Tanaka, Frauke Neff, Anna Saran, Martin R Larsen, Soile Tapio
Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer´s. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer´s model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates...
September 30, 2016: Oncotarget
Erin E Sundermann, Pauline M Maki, Leah H Rubin, Richard B Lipton, Susan Landau, Anat Biegon
OBJECTIVE: We investigated sex differences in verbal memory across different levels of neural dysfunction, measured by temporal lobe glucose metabolic rates (TLGluMR). METHODS: Three hundred ninety controls and 672 participants with amnestic mild cognitive impairment (aMCI) and 254 with Alzheimer disease (AD) dementia from the Alzheimer's Disease Neuroimaging Initiative completed the Rey Auditory Verbal Learning Test (RAVLT) and [(18)F]-fluorodeoxyglucose-PET. Cross-sectional analyses were conducted using linear regression to examine the sex by TLGluMR interaction on RAVLT performance in the overall sample and within diagnostic groups adjusting for age, education, and APOE ε4 genotype...
October 5, 2016: Neurology
Jean-Bastien Bott, Céline Héraud, Brigitte Cosquer, Karine Herbeaux, Julien Aubert, Maxime Sartori, Romain Goutagny, Chantal Mathis
: Brain mechanisms compensating for cerebral lesions may mitigate the progression of chronic neurodegenerative disorders such as Alzheimer's disease (AD). Mild cognitive impairment (MCI), which often precedes AD, is characterized by neuronal loss in the entorhinal cortex (EC). This loss leads to a hippocampal disconnection syndrome that drives clinical progression. The concomitant sprouting of cholinergic terminals in the hippocampus has been proposed to compensate for reduced EC glutamatergic input...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
P S Jairani, P M Aswathy, Srinivas Gopala, Joe Verghese, P S Mathuranath
BACKGROUND: This study delineates the role of the interaction of apolipoprotein E (APOE) and MAPT alleles in contributing to disease risks of dementia in a southern Indian population. METHODS: A sample of 419 patients comprising Alzheimer's disease (AD; n = 156), mild cognitive impairment (MCI; n = 87), frontotemporal dementia (FTD; n = 127), vascular dementia (VD; n = 37), and dementia with Lewy bodies (DLB; n = 12) was analysed in comparison with a control group (n = 138)...
October 6, 2016: Dementia and Geriatric Cognitive Disorders
Miguel Ángel Muñoz-Ruiz, Anette Hall, Jussi Mattila, Juha Koikkalainen, Sanna-Kaisa Herukka, Minna Husso, Tuomo Hänninen, Ritva Vanninen, Yawu Liu, Merja Hallikainen, Jyrki Lötjönen, Anne M Remes, Irina Alafuzoff, Hilkka Soininen, Päivi Hartikainen
BACKGROUND: Disease State Index (DSI) and its visualization, Disease State Fingerprint (DSF), form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. AIMS: To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD) and Alzheimer's disease (AD). METHODS: The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases...
May 2016: Dementia and Geriatric Cognitive Disorders Extra
Fan Zhu, Bharat Panwar, Hiroko H Dodge, Hongdong Li, Benjamin M Hampstead, Roger L Albin, Henry L Paulson, Yuanfang Guan
We present COMPASS, a COmputational Model to Predict the development of Alzheimer's diSease Spectrum, to model Alzheimer's disease (AD) progression. This was the best-performing method in recent crowdsourcing benchmark study, DREAM Alzheimer's Disease Big Data challenge to predict changes in Mini-Mental State Examination (MMSE) scores over 24-months using standardized data. In the present study, we conducted three additional analyses beyond the DREAM challenge question to improve the clinical contribution of our approach, including: (1) adding pre-validated baseline cognitive composite scores of ADNI-MEM and ADNI-EF, (2) identifying subjects with significant declines in MMSE scores, and (3) incorporating SNPs of top 10 genes connected to APOE identified from functional-relationship network...
October 5, 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 which 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...
October 4, 2016: Molecular Pharmaceutics
Alefiya Dhilla Albers, Josephine Asafu-Adjei, Mary K Delaney, Kathleen E Kelly, Teresa Gomez-Isla, Deborah Blacker, Keith A Johnson, Reisa A Sperling, Bradley T Hyman, Rebecca A Betensky, Lloyd Hastings, Mark W Albers
OBJECTIVE: To relate a novel test of identifying and recalling odor percepts to biomarkers of Alzheimer's Disease (AD) in well-characterized elderly individuals, ranging from cognitively normal to demented. METHODS: 183 participants (cognitively normal: n=70, subjective cognitive concerns: n=74, Mild Cognitive Impairment (MCI): n=29, AD dementia: n=10) were administered novel olfactory tests: the Odor Percept IDentification (OPID) and the Percepts of Odor Episodic Memory (POEM) tests...
October 1, 2016: Annals of Neurology
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