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Current Alzheimer Research

Marie Bruun, Kristian S Frederiksen, Hanneke F M Rhodius-Meester, Marta Baroni, Le Gjerum, Juha Koikkalainen, Timo Urhema, Antti Tolonen, Mark van Gils, Tong Tong, Daniel Rueckert, Nadia Dyremos, Birgitte Bo Andersen, Anja Hviid Simonsen, Afina Lemstra, Merja Hallikainen, Sudhir Kurl, Sanna-Kaisa Herukka, Anne M Remes, Gunhild Waldemar, Hilkka Soininen, Patrizia Mecocci, Wiesje M van der Flier, Jyrki Lötjönen, Steen G Hasselbalch
BACKGROUND: Determining the underlying etiology of dementia can be challenging. Computer-based clinical decision support systems (CDSS) have the potential to provide objective comparison of data and assist clinicians. OBJECTIVES: To assess the diagnostic impact of a CDSS, the PredictND tool, for differential diagnosis of dementia in memory clinics. METHOD: In this prospective multicenter study, we recruited 779 patients with either subjective cognitive decline (n=252), mild cognitive impairment (n=219) or any type of dementia (n=274) and followed them for minimum 12 months...
January 3, 2019: Current Alzheimer Research
Yan Hu, Guangya Zhou, Chi Zhang, Mengying Zhang, Qin Chen, Linfeng Zheng, Bing Niu
BACKGROUND: Alzheimer's disease swept every corner of the globe and the number of patients worldwide has been rising. At present, there are as many as 30 million people with Alzheimer's disease in the world, and it is expected to exceed 80 million people by 2050. Consequently, the study of Alzheimer's drugs has become one of the most popular medical topics. METHODS: In this study, in order to build predicting model for Alzheimer's drugs and targets. the attribute discriminator CfsSubsetEval, ConsistencySubsetEval and FilteredSubsetEval are combined with search methods such as BestFirst, GeneticSearch and Greedystepwise to filter the molecular descriptors...
January 3, 2019: Current Alzheimer Research
HBSc Ka Yi G Koo, Tom A Schweizer, Corinne E Fischer, David G Munoz
BACKGROUND: The Apolipoprotein (APOE) ε4 allele is a well-known risk factor for Alzheimer's Disease (AD), and sleep disturbances are commonly associated with AD. However, few studies have investigated the relationship between APOE ε4 and abnormal sleep patterns (N+) in AD. OBJECTIVE: To examine the relationship between APOE genotype, Lewy body pathology, and abnormal sleep patterns in a large group of subjects with known AD load evaluated upon autopsy. METHOD: Data from 2,368 cases obtained from the National Alzheimer's Coordinating Centre database were categorized as follows: Braak Stage V/VI and CERAD frequent neuritic plaques as high load AD, Braak Stage III/IV and moderate CERAD as intermediate load AD, and Braak Stage 0/I/II and infrequent CERAD as no to low load AD...
January 3, 2019: Current Alzheimer Research
Christian Humpel
Transgenic mice have been extensively used to study the Alzheimer pathology. In order to reduce, refine and replace (3Rs) the number of animals, ex vivo cultures are used and optimized. Organotypic brain slices are the most potent ex vivo slice culture models, keeping the 3-dimensional structure of the brain and being closest to the in vivo situation. Organotypic brain slice cultures have been used for many decades but were mainly prepared from postnatal (day 8-10) old rats or mice. More recent work (including our lab) now aims to culture organotypic brain slices from adult mice including transgenic mice...
December 12, 2018: Current Alzheimer Research
Ali Ezzati, Cuiling Wang, Mindy J Katz, Carol A Derby, Andrea R Zammit, Molly E Zimmerman, Jelena M Pavlovic, Martin J Sliwinski, Richard B Lipton
BACKGROUND: Chronic pain is common among older adults and is associated with cognitive dysfunction based on cross-sectional studies. However, the longitudinal association between chronic pain and incident dementia in community-based samples is unknown. OBJECTIVE: We aimed to evaluate the associations of pain intensity and pain interference with incident dementia in a community-based sample of older adults. METHODS: Participants were 1,114 individuals 70 years of age or older from Einstein Aging Study (EAS), a longitudinal cohort study of community-dwelling older adults in the Bronx County, NY...
December 12, 2018: Current Alzheimer Research
Chuntida Kamalashiran, Sombat Muengtaweepongsa, Junya Pattaraarchachai, Kusuma Sriyakul
BACKGROUND: Dementia is a common medical disorder in elderly. Oxidative stress plays a major role in the process of cognitive decline in dementia. Perilla seed oil demonstrates its neuroprotective effects via anti-oxidative mechanisms against dementia. We investigate neuroprotective effects of perilla seed oil as an additional treatment in patients with mild to moderate dementia. METHOD: A double-blind, randomized-control trial (perilla seed oil versus placebo) in patients with mild to moderate dementia was conducted...
December 12, 2018: Current Alzheimer Research
Wenjie Hu, Lin Wen, Fang Cao, Yexin Wang
Background:Alzheimer disease (AD) is a chronic progressive neurodegenerative disorder in central nervous system seen. OBJECTIVE: We aimed to study the miR-107 in Alzheimer's Disease (AD) pathology through regulating SYK and NF-κB signaling pathway. METHOD: Bioinformatics analysis was performed to screen NF-κB signaling pathway and differentially expressed genes. The target relationship between miR-107 and SYK was verified by dual luciferase assay. QRT-PCR and western blot analysis were used to verify the expression level of miR-107, SYK and NF-κB signaling pathway related proteins of hippocampus primary neurons...
December 12, 2018: Current Alzheimer Research
Ashwani Kumar, Vineet Mehta, Utkarsh Raj, Pritish Kumar Varadwaj, Malairaman Udayabanu, Ragothaman M Yennamalli, Tiratha Raj Singh
BACKGROUND: Cholinesterase inhibitors are the first line of therapy for the management of Alzheimer's disease (AD), however, it is now established that they provide only temporary and symptomatic relief, besides, having several inherited side-effects. Therefore, an alternative drug discovery method is to identify new and safer 'disease-modifying drugs'. METHODS: Herein, we screened 646 small molecules of natural origin having reported pharmacological and functional values through in-silico docking studies to predict safer neuromodulatory molecules with potential to modulate acetylcholine metabolism...
December 12, 2018: Current Alzheimer Research
Aidan R O'Mara, Jessica M Collins, Anna E King, James C Vickers, Matthew T K Kirkcaldie
BACKGROUND: Images of amyloid-β pathology characteristic of Alzheimer's disease are difficult to consistently and accurately segment, due to diffuse deposit boundaries and imaging variations. METHODS: We evaluated the performance of ImageSURF, our open-source ImageJ plugin, which considers a range of image derivatives to train image classifiers. We compared ImageSURF to standard image thresholding to assess its reproducibility, accuracy and generalizability when used on fluorescence images of amyloid pathology...
December 12, 2018: Current Alzheimer Research
Bruno De Araujo Herculano, Zhe Wang, Weihong Song
BACKGROUND: Deposition of the amyloid β protein (Aβ) into neuritic plaques is the neuropathological hallmark of Alzheimer's Disease (AD). Aβ is generated through the cleavage of the Amyloid Precursor Protein (APP) by β-secretase and γ-secretase. Currently, the evaluation of APP cleavage by β-secretase in experimental settings has largely depended on models that do not replicate the physiological conditions of this process. OBJECTIVE: To establish a novel live cell-based β-secretase enzymatic assay utilizing a novel chimeric protein that incorporates the natural sequence of APP and more closely replicates its cleavage by β-secretase under physiological conditions...
December 12, 2018: Current Alzheimer Research
Bin Zhou, Qianhua Zhao, Shinsuke Kojima, Ding Ding, Satoshi Higashide, Yoji Nagai, Qihao Guo, Tatsuo Kagimura, Masanori Fukushima, Zhen Hong
BACKGROUND & OBJECTIVE: The purpose of this study is to identify the risk factors associated with the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia for the early detection of AD. METHODS: The study comprised a prospective cohort study that included 400 MCI subjects with annual follow-ups for 3 years. RESULTS: During the first 12 months' follow-up, 42 subjects converted to Alzheimer's dementia (21 probable AD and 21 possible AD), two subjects converted to other types of dementia and 56 subjects lost follow...
November 28, 2018: Current Alzheimer Research
Prapimpun Wongchitrat, Nattaporn Pakpian, Kuntida Kitidee, Kamonrat Phopin, Pornpatr A Dharmasaroja, Piyarat Govitrapong
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in elderly populations. Changes in the expression of amyloid precursor protein (APP)-cleaving enzymes directly affect the formation of amyloid beta (Aβ) plaques, a neuropathological hallmark of AD. OBJECTIVE: We used peripheral blood from AD patients to investigate the expression of genes related to APP-processing [(β-site APP-cleaving enzyme 1 (BACE1), presenilin1 (PSEN1), and a disintegrin and metalloproteinase family 10 (ADAM10) and 17 (ADAM17)] and the epigenetic genes sirtuin (SIRT)1-3, which regulate Aβ production...
November 8, 2018: Current Alzheimer Research
Xing Li, Xiaoqin Run, Zhen Wei, Kuan Zeng, Zhihou Liang, Fang Huang, Dan Ke, Qun Wang, Jian-Zhi Wang, Rong Liu, Bin Zhang, Xiaochuan Wang
BACKGROUND: Preclinical and clinical evidences suggest that elderly individuals are at increased risk of cognitive decline after general anesthesia. General anesthesia is also believed to be a risk factor for postoperative cognitive dysfunction (POCD) and Alzheimer's disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials. However, how insulin treatment improves cognitive function is poorly understood...
October 31, 2018: Current Alzheimer Research
Vladimiro Artuso, Luisa Benussi, Roberta Ghidoni, Soraya Moradi-Bachiller, Federica Fusco, Stefano Curtolo, Ignazio Roiter, Gianluigi Forloni, Diego Albani
BACKGROUND: Presenilin-1 (PSEN-1) is a component of the g-secretase complex involved in b-amyloid precursor protein (AbPP) processing. Usually Alzheimer's disease (AD)-linked mutations in the PSEN-1 gene lead to early onset and increase the production of the aggregation-prone peptide Ab42. However, the PSEN-1 E318G variant has an unclear pathogenic role, and was recently reported as a genetic risk factor for AD. In particular, E318G variant presence correlated with increased cerebrospinal fluid (CSF) levels of total tau (t-tau) and phosphorylated tau (p-tau)...
October 31, 2018: Current Alzheimer Research
Maxime François, Caroline Felicity Bull, Michael Felix Fenech, Wayne Richard Leifert
INTRODUCTION: Aging is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases such as Alzheimer's disease (AD). AD is a progressive degenerative disorder of the brain and is the most common form of dementia. METHODS: To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease...
October 21, 2018: Current Alzheimer Research
Yaojing Chen, Di Qi, Ting Qin, Kewei Chen, Meishan Ai, Xin Li, He Li, Junying Zhang, Haohao Mao, Yiru Yang, Zhanjun Zhang
BACKGROUND: Among the protective factors for cognitive decline related to aging and Alzheimer's disease, education level is one of the most prominent. However, the mechanisms underlying the protective effects of education on cognition remain to be elucidated. In this study, we aimed to systematically assess the role of functional connectivity (FC) of resting-state brain networks playing in the cognition-protection effect of education. METHODS: Data from a battery of neuropsychological tests and functional magnetic resonance imaging in resting-state were acquired in 77 cognitively normal elderly participants from local communities in Beijing, China...
October 21, 2018: Current Alzheimer Research
Zhenkui Ren, Mei Yang, Zhizhong Guan, Wenfeng Yu
Background β-amyloid (Aβ) aggregation plays an important role in the pathogenesis of Alzheimer's disease (AD), and astrocytes can significantly inhibit Aβ aggregation. Astrocytic α7 neuronal nicotinic acetylcholine receptor (nAChR) upregulation detected in AD brains was closely associated with Aβ deposits. However, the relationships between the astrocytic α7 nAChRs and Aβ aggregation remain unclear. Methods The Aβ oligomers levels in astrocytic cell lysates and culture medium were measured after treatment with nicotine or co-treatment with a phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) inhibitor...
October 21, 2018: Current Alzheimer Research
J Stenzel, C Ruhlmann, T Lindner, S Polei, S Teipel, J Kurth, A Rominger, B J Krause, B Vollmar, A Kuhla
BACKGROUND: Positron-emission-tomography (PET) using 18F labeled florbetaben allows non-invasive in vivo-assessment of amyloid beta (Aβ), a pathological hallmark of Alzheimer's disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques...
October 21, 2018: Current Alzheimer Research
Cassandra Morrison, Sheida Rabipour, Vanessa Taler, Christine Sheppard, Frank Knoefel
BACKGROUND: Cognitive deficits are correlated with increasing age and become more pronounced for people with mild cognitive impairment (MCI) and dementia caused by Alzheimer's disease (AD). Conventional methods to diagnose cognitive decline (i.e., neuropsychological testing and clinical judgment) can lead to false positives. Tools such as electroencephalography (EEG) offer more refined, objective measures of indexing electrophysiological changes associated with healthy aging, MCI, and AD...
October 21, 2018: Current Alzheimer Research
Tadanori Hamano, Kouji Hayashi, Norimichi Shirafuji, Yasunari Nakamoto
The pathogenic mechanisms of Alzheimer's disease (AD) involve the deposition of abnormally misfolded proteins, amyloid β protein (Aβ) and tau protein. Aβ comprises senile plaques, and tau aggregates form neurofibrillary tangles (NFTs), both of which are hallmarks of AD. Autophagy is the main conserved pathway for the degeneration of aggregated proteins, Aβ ,tau and dysfunctional organelles in the cell. Many animal model studies have demonstrated that autophagy normally functions as the protective factor against AD progression associated with intracytoplasmic toxic Aβ and tau aggregates...
October 4, 2018: Current Alzheimer Research
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