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https://www.readbyqxmd.com/read/28734998/oxidative-stress-with-tau-hyperphosphorylation-in-memory-impaired-1-2-diacetylbenzene-treated-mice
#1
Sin-Woo Kang, Sung Jin Kim, Min-Sun Kim
Long-term exposure to organic solvent may be related to the incidence of neuronal diseases, such as, Alzheimer's disease, depression, multiple sclerosis, dementia, Parkinson's disease. Previously, the authors reported 1,2-diacetylbenzene (DAB; a neurotoxic metabolite of 1,2-diethylbenzene) causes central and peripheral neuropathies that lead to motor neuronal deficits. Furthermore, it is known DAB increases oxidative stress and protein adduct levels and impairs hippocampal neurogenesis in mice. The authors examined the relevance of oxidative stress and tau hyperphosphorylation in the hippocampus...
July 19, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28734699/an-update-on-the-genetics-of-dementia-with-lewy-bodies
#2
REVIEW
Leonie J M Vergouw, Inger van Steenoven, Wilma D J van de Berg, Charlotte E Teunissen, John C van Swieten, Vincenzo Bonifati, Afina W Lemstra, Frank Jan de Jong
The genetic architecture of dementia with Lewy bodies (DLB) is increasingly taking shape. Initially, genetic research focused mainly on linkage and candidate gene studies in small series of DLB patients. More recently, association and exome sequencing studies in larger groups have been conducted, and have shown that several variants in GBA and the APOE ε4 allele are important genetic risk factors for DLB. However, genetic research in DLB is still in its infancy. So far, many genetic studies have been biased and performed in clinically and pathologically heterogeneous populations...
July 13, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28734271/development-and-validation-of-sensitive-lc-ms-ms-method-for-the-quantification-of-suvn-502-and-its-metabolite-and-its-application-for-first-in-human-pharmacokinetic-study
#3
Ramakrishna Nirogi, Devender Reddy Ajjala, Raghupathi Aleti, Lakshmiprasanna Rayapati, Hanumanth Rao Pantangi, Rajesh Kumar Boggavarapu, Naga Surya Prakash Padala
A sensitive and rapid LC-MS/MS method was developed and validated for the quantification of SUVN-502 and M1 of SUVN-502, a 5-HT6 receptor antagonist for the treatment of dementia associated with Alzheimer's disease. Following solid-phase extraction, SUVN-502 and M1 of SUVN-502 and IS were eluted with 10mM ammonium acetate (pH 4.0) and acetonitrile using a rapid gradient program on reverse phase column. Multiple reaction monitoring mode was used to monitor the respective transitions of m/z 478.2→377.7 for SUVN-502 and m/z 464...
April 14, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28734089/dementia-risk-and-prevention-by-targeting-modifiable-vascular-risk-factors
#4
REVIEW
Sana Tariq, Philip A Barber
The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that leads to brain atrophy years before symptoms manifest. Currently, no cure exists and extensive efforts are being made to mitigate cognitive impairment in late life in order to reduce the burden on patients, caregivers, and society. The most common type of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) often co-exists in the brain and shares common, modifiable risk factors, which are targeted in numerous secondary prevention trials...
July 22, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28734058/evaluation-of-2-benzylidene-1-tetralone-derivatives-as-antagonists-of-a1-and-a2a-adenosine-receptors
#5
Lesetja J Legoabe, Mietha M Van der Walt, Gisella Terre'Blanche
Antagonists of the adenosine receptors (A1 and A2A ) are thought to be beneficial in neurological disorders, such as Alzheimer's and Parkinson's disease. The aim of this study was to explore 2-benzylidene-1-tetralone derivatives as antagonists of A1 and/or A2A adenosine receptors. In general, the test compounds were found to be selective for the A1 adenosine receptor, with only three test compounds possessing affinity for both the A1 and A2A adenosine receptor. The 2-benzylidene-1-tetralones bearing a hydroxyl substituent at either position C5, C6 or C7 of ring A displayed favorable adenosine A1 receptor binding, while C5 hydroxy substitution led to favorable A2A adenosine receptor affinity...
July 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28733961/a-review-of-biomarkers-for-neurodegenerative-disease-will-they-swing-us-across-the-valley
#6
REVIEW
Thomas G Beach
Measures of the severity of cognitive impairment or parkinsonism are the usual endpoints in clinical trials for Alzheimer's disease (AD) and Parkinson's disease (PD), but are critically hampered by their lack of disease sensitivity and specificity. Due to the high failure rate of clinical trials, the rate of regulatory approval for efficacious new drugs has stagnated in the past few decades, with the gap between basic science discovery and clinical application metaphorically termed the "Valley of Death". While the causes for this are probably multiple and complex, the usage of biomarkers as surrogate endpoints, particularly when they are molecularly-specific for the disease, has achieved some success in cancer trials, and it is likely that neurodegenerative disease trials would benefit from the same approach...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733960/a-review-of-fluid-biomarkers-for-alzheimer-s-disease-moving-from-csf-to-blood
#7
REVIEW
Kaj Blennow
A set of core cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) includes total tau (T-tau), phosphorylated tau (P-tau) and β-amyloid 42 (Aβ42). These biomarkers reflect some of the key aspects of AD pathophysiology, including neuronal degeneration, tau phosphorylation with tangle formation, and Aβ aggregation with deposition of the peptide into plaques. The core AD CSF biomarkers have been validated clinically in numerous studies, and found to have a very high diagnostic performance to identify AD, both in the dementia and in the mild cognitive impairment stages of the disease...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733959/increasing-precision-of-clinical-diagnosis-of-alzheimer-s-disease-using-a-combined-algorithm-incorporating-clinical-and-novel-biomarker-data
#8
REVIEW
Marwan N Sabbagh, Lih-Fen Lue, Daniel Fayard, Jiong Shi
Establishing the in vivo diagnosis of Alzheimer's disease (AD) or other dementias relies on clinical criteria; however, the accuracy of these criteria can be limited. The diagnostic accuracy is 77% for a clinical diagnosis of AD, even among experts. We performed a review through PubMed of articles related to specific diagnostic modalities, including APOE genotyping, cerebrospinal fluid (CSF) testing, fludeoxyglucose F 18 positron emission tomography (PET), amyloid PET, tau PET, computed tomography (CT), single-photon emission CT, magnetic resonance imaging (MRI), and B12 and thyroid-stimulating hormone screening, to determine the specificity and sensitivity of each test used in the clinical diagnosis of AD...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733955/detection-of-plasma-biomarkers-using-immunomagnetic-reduction-a-promising-method-for-the-early-diagnosis-of-alzheimer-s-disease
#9
REVIEW
Shieh-Yueh Yang, Ming-Jang Chiu, Ta-Fu Chen, Herng-Er Horng
Alzheimer's disease (AD) is the most common form of dementia. The development of assay technologies able to diagnose early-stage AD is important. Blood tests to detect biomarkers, such as amyloid and total Tau protein, are among the most promising diagnostic methods due to their low cost, low risk, and ease of operation. However, such biomarkers in blood occur at extremely low levels and are difficult to detect precisely. In the early 2000s, a highly sensitive assay technology, immunomagnetic reduction (IMR), was developed...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733814/neuroprotective-effect-of-ipriflavone-against-scopolamine-induced-memory-impairment-in-rats
#10
Hani S Hafez, Doaa A Ghareeb, Samar R Saleh, Mariam M Abady, Maha A El Demellawy, Hend Hussien, Nihad Abdel-Monem
BACKGROUND: Alzheimer's disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors...
July 22, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28731452/temporal-order-of-alzheimer-s-disease-related-cognitive-marker-changes-in-blsa-and-wrap-longitudinal-studies
#11
Murat Bilgel, Rebecca L Koscik, Yang An, Jerry L Prince, Susan M Resnick, Sterling C Johnson, Bruno M Jedynak
Investigation of the temporal trajectories of currently used neuropsychological tests is critical to identifying earliest changing measures on the path to dementia due to Alzheimer's disease (AD). We used the Progression Score (PS) method to characterize the temporal trajectories of measures of verbal memory, executive function, attention, processing speed, language, and mental status using data spanning normal cognition, mild cognitive impairment, and AD from 1,661 participants with a total of 7,839 visits (age at last visit 77...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731449/cerebrospinal-fluid-neurogranin-as-a-biomarker-of-neurodegenerative-diseases-a-cross-sectional-study
#12
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Robert Nisticò, Roberto Floris, Francesco Garaci, Harald Hampel
We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n = 35), FTD (n = 9), MCI (n = 41), cognitively HC (n = 23)]...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731446/effect-of-apoe-genotype-on-synaptic-proteins-in-earlier-adult-life
#13
Lindsey I Sinclair, Seth Love
BACKGROUND: Possession of APOEɛ4 is a strong risk factor for late-onset Alzheimer's disease and is associated with loss of synaptic proteins in the elderly even in the absence of Alzheimer's disease. OBJECTIVE: We hypothesized that ɛ4 allele possession in non-demented adults aged under-75 would also be associated with alterations in the levels of synaptic proteins. METHODS: We measured synaptophysin, PSD95, drebrin, SNAP-25, and septin 7 by ELISA in hippocampus and superior temporal gyrus from 103 adults aged <75 without dementia...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731445/colivelin-ameliorates-impairments-in%C3%A2-cognitive-behaviors-and-synaptic-plasticity-in-app-ps1-transgenic-mice
#14
Meina Wu, Hui Shi, Yexin He, Li Yuan, Xuesong Qu, Jun Zhang, Zhaojun Wang, Hongyan Cai, Jinshun Qi
Alzheimer's disease (AD) is the most common cause of dementia, and effective therapeutics are lacking. Colivelin (CLN), a novel, strong humanin derivative, is effective in vitro in preventing cell death induced by AD-causative genes and amyloid-β protein (Aβ) even at a low concentration. We recently demonstrated that intrahippocampal injection of CLN prevents Aβ25-35-induced deficits in spatial memory and synaptic plasticity in normal rats. Here, we further observed the effects of chronically intranasally (i...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731443/accuracy-of-clinical-diagnosis-of-dementia-with-lewy-bodies-versus-neuropathology
#15
Ragnhild E Skogseth, Tibor Hortobágyi, Hogne Soennesyn, Luiza Chwiszczuk, Dominic Ffytche, Arvid Rongve, Clive Ballard, Dag Aarsland
BACKGROUND: The first consensus criteria for dementia with Lewy bodies (DLB) published in 1996 were revised in 2005, partly because the original clinical criteria had suboptimal sensitivity. Few studies have assessed the accuracy of the 2005 criteria applied prospectively in newly diagnosed patients who have been followed longitudinally. OBJECTIVE: To explore the correlation between clinical and pathological diagnoses in patients with DLB and Parkinson's disease with dementia (PDD)...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731440/challenges-and-considerations-related-to-studying-dementia-in-african-americans
#16
Eseosa T Ighodaro, Peter T Nelson, Walter A Kukull, Frederick A Schmitt, Erin L Abner, Allison Caban-Holt, Shoshana H Bardach, Derrick C Hord, Crystal M Glover, Gregory A Jicha, Linda J Van Eldik, Alexander X Byrd, Anita Fernander
Blacks/African Americans have been reported to be ∼2-4 times more likely to develop clinical Alzheimer's disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731435/identification-of-circulating-mir-125b-as-a-potential-biomarker-of-alzheimer-s-disease-in-app-ps1-transgenic-mouse
#17
Honghai Hong, Yang Li, Baochang Su
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive decline in cognitive abilities of the affected individuals. Biological markers are essential to identify individuals at early stages of the disease for timely therapeutic intervention. Currently, pathological biomarkers are detected either through cerebrospinal fluid analysis or brain imaging, or postmortem, all of which are expensive, invasive, or time consuming. Recently, some studies have shown that circulating miR-125b, miR-181c, miR-9, miR-191-5p, miR-26b-3p, and miR-28-3p may be biomarkers of AD...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731429/severity-of-depression-impacts-imminent-conversion-from-mild-cognitive-impairment-to-alzheimer-s-disease
#18
Michaela Defrancesco, Josef Marksteiner, Georg Kemmler, Walter Wolfgang Fleischhacker, Imrich Blasko, Eberhard A Deisenhammer
BACKGROUND: Mild cognitive impairment (MCI) has been suggested to represent a prodromal stage of dementia and to confer a high risk for conversion to dementia Alzheimer's type (DAT). OBJECTIVES: In this study, we examined the predictive value of depressive symptoms and neuropsychological variables on conversion of MCI to DAT. METHODS: Neuropsychological and clinical follow-up data of 260 MCI patients seen at the Psychiatric Memory Clinic of the Medical University of Innsbruck between 2005 and 2015 were analyzed retrospectively...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731362/greater-cognitive-deficits-with-sleep-disordered-breathing-among-individuals-with-genetic-susceptibility-to-alzheimer-s-disease-the-multi-ethnic-study-of-atherosclerosis
#19
Dayna A Johnson, Jacqueline Lane, Rui Wang, Michelle Reid, Ina Djonlagic, Annette L Fitzpatrick, Stephen R Rapp, Luenda E Charles, Ruth O'Hara, Richa Saxena, Susan Redline
RATIONALE: There are conflicting findings regarding the link between sleep apnea and cognitive dysfunction. OBJECTIVE: Investigate associations between indicators of sleep-disordered breathing (SDB) and cognitive function in the Multi-Ethnic Study of Atherosclerosis and assess effect modification by the apolipoprotein ε-4 (APOE-ε4) allele. METHODS: A diverse population (N=1,752) underwent Type 2 in-home polysomnography, which included measurement of % sleep time <90% oxyhemoglobin saturation (%Sat<90%) and apnea-hypopnea index (AHI)...
July 21, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28731260/transcriptional-regulation-of-app-by-apoe-to-boldly-go-where-no-isoform-has-gone-before-apoe-app-transcription-and-ad-hypothesised-mechanisms-and-existing-knowledge-gaps
#20
REVIEW
Liying Corinne Lee, Michele Q L Goh, Edward H Koo
Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti-amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β-protein and its precursor, the amyloid precursor protein (APP) are but a part of the disease cascade. Further, risk of AD can be modulated by a number of factors, the most impactful being the ɛ4 isoform of apolipoprotein E (apoE)...
July 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
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