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https://www.readbyqxmd.com/read/28655134/multiple-mechanisms-linking-type-2-diabetes-and-alzheimer-s-disease-testosterone-as-a-modifier
#1
Prita R Asih, Michelle L Tegg, Hamid Sohrabi, Malcolm Carruthers, Samuel E Gandy, Farid Saad, Giuseppe Verdile, Lars M Ittner, Ralph N Martins
Evidence in support of links between type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has increased considerably in recent years. AD pathological hallmarks include the accumulation of extracellular amyloid-β (Aβ) and intracellular hyperphosphorylated tau in the brain, which are hypothesized to promote inflammation, oxidative stress, and neuronal loss. T2DM exhibits many AD pathological features, including reduced brain insulin uptake, lipid dysregulation, inflammation, oxidative stress, and depression; T2DM has also been shown to increase AD risk, and with increasing age, the prevalence of both conditions increases...
June 22, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28649025/a%C3%AE-plaque-selective-nir-fluorescence-probe-to-differentiate-alzheimer-s-disease-from-tauopathies
#2
K Rajasekhar, Nagarjun Narayanaswamy, N Arul Murugan, Keith Viccaro, Hyoung-Gon Lee, Kavita Shah, Thimmaiah Govindaraju
Selective detection and staining of toxic amyloid plaques, a potential biomarker present in the Alzheimer's disease (AD) brain is crucial for both clinical diagnosis and monitoring AD disease progression. Herein, we report a coumarin-quinoline (CQ) conjugate-based turn-on near-infrared (NIR) fluorescence probe for specific detection of β-amyloid (Aβ) aggregates. CQ probe is highly sensitive and exhibits ~100-fold fluorescence enhancement in vitro upon binding Aβ aggregates with enhanced quantum yield. Furthermore, the probe has ~10-fold higher binding affinity towards Aβ aggregates (86nM) compared to commonly used Thioflavin T...
June 17, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28643852/therapeutic-d2-3-receptor-occupancies-and-response-with-low-amisulpride-blood-concentrations-in-very-late-onset-schizophrenia-like-psychosis-vloslp
#3
Suzanne Reeves, Kate Eggleston, Elizabeth Cort, Emma McLachlan, Stuart Brownings, Akshay Nair, Suki Greaves, Alan Smith, Joel Dunn, Paul Marsden, Robert Kessler, David Taylor, Julie Bertrand, Robert Howard
OBJECTIVE: Antipsychotic drug sensitivity in very late-onset schizophrenia-like psychosis (VLOSLP) is well documented, but poorly understood. This study aimed to investigate blood drug concentration, D2/3 receptor occupancy and outcome in VLOSLP during open amisulpride prescribing, and compare this with Alzheimer's disease (AD). METHODS: Blood drug concentration, prolactin, symptoms and extrapyramidal side-effects (EPS) were serially assessed during dose titration...
June 23, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28632523/frontotemporal-dementia-presenting-as-gambling-disorder-when-a-psychiatric-condition-is-the-clue-to-a-neurodegenerative-disease
#4
Giacomo Tondo, Fabiola De Marchi, Emanuela Terazzi, Marta Sacchetti, Roberto Cantello
Behavioral variant frontotemporal dementia, the most common form of frontotemporal dementia, is characterized by executive dysfunction and changes in personality and behavior, sometimes with associated psychiatric disorders. We report a man who suddenly developed a gambling disorder when he was 55 years old. A year later he developed personality changes of agitation, euphoria, and disinhibition, along with binge eating and dysthymia. He did not improve on paroxetine 40 mg/day. Two years after the onset of his symptoms, he came to our clinic for evaluation...
June 2017: Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology
https://www.readbyqxmd.com/read/28628634/protein-signature-in-cerebrospinal-fluid-and-serum-of-alzheimer-s-disease-patients-the-case-of-apolipoprotein-a-1-proteoforms
#5
Chiara Fania, Beatrice Arosio, Daniele Capitanio, Enrica Torretta, Cristina Gussago, Evelyn Ferri, Daniela Mari, Cecilia Gelfi
In the diagnosis of Alzheimer's disease (AD) total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and the 42 amino acid isoform of alpha β-amyloid (Aβ) are well established surrogate CSF markers. However, there is a constant need for new diagnostic markers to identify the disease at a very early stage. The identification of new molecules for AD diagnosis and monitoring in CSF is hampered by several "confounding" factors including intra- and inter-individual, pre-analytical and analytical variabilities...
2017: PloS One
https://www.readbyqxmd.com/read/28627905/mind-wandering-in-healthy-aging-and-early-stage-alzheimer-s-disease
#6
Mate Gyurkovics, David A Balota, Jonathan D Jackson
OBJECTIVE: The frequency of mind-wandering (MW) decreases as a function of age in healthy individuals. One possible explanation is that MW is a resource-dependent process, and cognitive resources decline with age. The present study provides the first investigation of MW in the earliest stages of Alzheimer's disease (AD) to further examine the resource model and discontinuities between healthy aging and AD. METHOD: Three large cohorts completed the Sustained Attention to Response Task (SART): a healthy middle-aged group (mean age = 61...
June 19, 2017: Neuropsychology
https://www.readbyqxmd.com/read/28626469/serum-amino-acid-profiles-in-normal-subjects-and-in-patients-with-or-at-risk-of-alzheimer-dementia
#7
Gaetano Corso, Adriana Cristofano, Nadia Sapere, Giancarlo la Marca, Antonella Angiolillo, Michela Vitale, Roberto Fratangelo, Teresa Lombardi, Carola Porcile, Mariano Intrieri, Alfonso Di Costanzo
BACKGROUND/AIMS: Abnormalities in the plasma amino acid profile have been reported in Alzheimer disease (AD), but no data exist for the prodromal phase characterized by subjective memory complaint (SMC). It was our aim to understand if serum amino acid levels change along the continuum from normal to AD, and to identify possible diagnostic biomarkers. METHODS: Serum levels of 15 amino acids and 2 organic acids were determined in 4 groups of participants - 29 with probable AD, 18 with mild cognitive impairment (MCI), 24 with SMC, and 46 cognitively healthy subjects (HS) - by electrospray tandem mass spectrometry...
January 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/28617434/lispro-mitigates-%C3%AE-amyloid-and-associated-pathologies-in-alzheimer-s-mice
#8
Ahsan Habib, Darrell Sawmiller, Song Li, Yang Xiang, David Rongo, Jun Tian, Huayan Hou, Jin Zeng, Adam Smith, Shengnuo Fan, Brian Giunta, Takashi Mori, Glenn Currier, Douglas Ronald Shytle, Jun Tan
Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer's disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li2CO3)...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28612291/-f-18-av-1451-binding-correlates-with-postmortem-neurofibrillary-tangle-braak-staging
#9
Marta Marquié, Michael Siao Tick Chong, Alejandro Antón-Fernández, Eline E Verwer, Nil Sáez-Calveras, Avery C Meltzer, Prianca Ramanan, Ana C Amaral, Jose Gonzalez, Marc D Normandin, Matthew P Frosch, Teresa Gómez-Isla
[F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer's disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET studies show that patients with mild cognitive impairment and AD dementia exhibit significantly higher in vivo [F-18]-AV-1451 retention than cognitively normal controls. Importantly, PET patterns of [F-18]-AV-1451 correlate well with disease severity and seem to match the predicted topographic Braak staging of neurofibrillary tangles (NFTs) in AD, although this awaits confirmation...
June 13, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28604243/the-use-of-cerebrospinal-fluid-biomarkers-to-measure-change-in-neurodegeneration-in-alzheimer-s-disease-clinical-trials
#10
Bob Olsson, Jonathan M Schott, Kaj Blennow, Henrik Zetterberg
All recent phase 3 trials of potentially disease-modifying therapies for Alzheimer's disease (AD) have so far failed. Potential reasons include enrolling subjects whose disease is too advanced or who do not have AD pathology, or simply incorrect drug targets. The goal of disease-modifying AD trials is to halt the progress of neuronal damage and death and this can be assessed in vivo using cerebrospinal fluid (CSF) biomarkers. Areas covered: The authors conducted a literature search of the use of CSF biomarkers in disease-modifying AD clinical trials using PubMed...
June 19, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28600952/time-course-of-tau-toxicity-and-pharmacologic-prevention-in-a-cell%C3%A2-model-of-tauopathy
#11
Marcus Pickhardt, Jacek Biernat, Sabrina Hübschmann, Frank J A Dennissen, Thomas Timm, Annukka Aho, Eva-Maria Mandelkow, Eckhard Mandelkow
The aggregation of Tau protein is a hallmark of neurodegenerative diseases including Alzheimer's disease. Previously, we generated a cell model of tauopathy based on the 4-repeat domain with the FTDP-17 mutation ΔK280 (Tau(4RDΔK)) which is expressed in a regulatable fashion (tet-on). The deletion variant ΔK280 is highly amyloidogenic and forms fibrous aggregates in neuroblastoma N2a cells staining with the reporter dye Thioflavin S. The aggregation of Tau(4RDΔK) is toxic, contrary to wildtype or anti-aggregant variants of the protein...
May 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28596505/progressive-modulation-of-the-human-olfactory-bulb-transcriptome-during-alzheimer%C3%A2-s-disease-evolution-novel-insights-into-the-olfactory-signaling-across-proteinopathies
#12
Mercedes Lachen-Montes, María Victoria Zelaya, Víctor Segura, Joaquín Fernández-Irigoyen, Enrique Santamaría
Alzheimer´s disease (AD) is characterized by progressive dementia, initially presenting olfactory dysfunction. Despite the olfactory bulb (OB) is the first central structure of the olfactory pathway, we lack a complete molecular characterization of the transcriptional events that occurs in this olfactory area during AD progression. To address this gap in knowledge, we have assessed the genome-wide expression in postmortem OBs from subjects with varying degree of AD pathology. A stage-dependent deregulation of specific pathways was observed, revealing transmembrane transport, and neuroinflammation as part of the functional modules that are disrupted across AD grading...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28582770/the-protective-effect-of-epimedii-folium-and-curculiginis-rhizoma-on-alzheimer-s-disease-by-the-inhibitions-of-nf-%C3%AE%C2%BAb-mapk-pathway-and-nlrp3-inflammasome
#13
Zhou Lan, Guangjing Xie, Meng Wei, Ping Wang, Lvyi Chen
The purpose of the current study was to explore the effects of the water extracts of Epimedii Folium and Curculiginis Rhizoma (EX) on Aβ-induced Alzheimer's disease. Aβ1-42 was stereotaxically injected bilaterally into the dorsal hippocampus, and then the rats were orally received EX at the doses of 2 g/kg and 6 g/kg for 30 days. Behavior was monitored through Morris water maze test. The neuroprotective effect of EX were examined with methods of histochemistry and biochemistry. EX reduced the contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and cortex...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28577254/the-value-of-whole-brain-ct-perfusion-imaging-and-ct-angiography-using-a-320-slice-ct-scanner-in-the-diagnosis-of-mci-and-ad-patients
#14
Bo Zhang, Guo-Jun Gu, Hong Jiang, Yi Guo, Xing Shen, Bo Li, Wei Zhang
OBJECTIVES: To validate the value of whole-brain computed tomography perfusion (CTP) and CT angiography (CTA) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: Whole-brain CTP and four-dimensional CT angiography (4D-CTA) images were acquired in 30 MCI, 35 mild AD patients, 35 moderate AD patients, 30 severe AD patients and 50 normal controls (NC). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and correlation between CTP and 4D-CTA were analysed...
June 2, 2017: European Radiology
https://www.readbyqxmd.com/read/28576172/multimodal-pet-imaging-of-amyloid-and-tau-pathology-in-alzheimer-disease-and-non-alzheimer-disease-dementias
#15
REVIEW
Chenjie Xia, Bradford C Dickerson
Biomarkers of the molecular pathology underpinning dementia syndromes are increasingly recognized as crucial for diagnosis and development of disease-modifying treatments. Amyloid PET imaging is an integral part of the diagnostic assessment of Alzheimer disease. Its use has also deepened understanding of the role of amyloid pathology in Lewy body disorders and aging. Tau PET imaging is an imaging biomarker that will likely play an important role in the diagnosis, monitoring, and treatment in dementias. Using tau PET imaging to examine how tau pathology relates to amyloid and other markers of neurodegeneration will serve to better understand the pathophysiologic cascade that leads to dementia...
July 2017: PET Clinics
https://www.readbyqxmd.com/read/28567666/serum-protein-based-profiles-as-novel-biomarkers-for-the-diagnosis-of-alzheimer-s-disease
#16
Shu Yu, Yue-Ping Liu, Hai-Liang Liu, Jie Li, Yang Xiang, Yu-Hui Liu, Shu-Sheng Jiao, Lu Liu, Yajiang Wang, Weiling Fu
As a multi-stage disorder, Alzheimer's disease (AD) is quickly becoming one of the most prevalent neurodegenerative diseases worldwide. Thus, a non-invasive, serum-based diagnostic platform is eagerly awaited. The goal of this study was to identify a serum-based biomarker panel using a predictive protein-based algorithm that is able to confidently distinguish AD patients from control subjects. One hundred and fifty-six patients with AD and the same number of gender- and age-matched control participants with standardized clinical assessments and neuroimaging measures were evaluated...
May 31, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28564579/lipid-membranes-catalyse-the-fibril-formation-of-the-amyloid-%C3%AE-1-42-peptide-through-lipid-fibril-interactions-that-reinforce-secondary-pathways
#17
David J Lindberg, Emelie Wesén, Johan Björkeroth, Sandra Rocha, Elin K Esbjörner
Alzheimer's disease is associated with the aggregation of amyloid-β (Aβ) peptides into oligomers and fibrils. Herein we explore how model lipid membranes modulate the rate and mechanisms of Aβ(1-42) self-assembly, in order to shed light on how this pathological reaction, may occur in the lipid-rich environments that this peptide encounters in the brain. Using a combination of in vitro biophysical experiments and theoretical approaches, we show that zwitterionic lipid vesicles accelerate the Aβ(1-42) fibril growth rate by interacting specifically with the growing fibrils...
May 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28560160/application-of-calibrated-fmri-in-alzheimer-s-disease
#18
Isabelle Lajoie, Scott Nugent, Clément Debacker, Kenneth Dyson, Felipe B Tancredi, AmanPreet Badhwar, Sylvie Belleville, Yan Deschaintre, Pierre Bellec, Julien Doyon, Christian Bocti, Serge Gauthier, Douglas Arnold, Marie-Jeanne Kergoat, Howard Chertkow, Oury Monchi, Richard D Hoge
Calibrated fMRI based on arterial spin-labeling (ASL) and blood oxygen-dependent contrast (BOLD), combined with periods of hypercapnia and hyperoxia, can provide information on cerebrovascular reactivity (CVR), resting blood flow (CBF), oxygen extraction fraction (OEF), and resting oxidative metabolism (CMRO2). Vascular and metabolic integrity are believed to be affected in Alzheimer's disease (AD), thus, the use of calibrated fMRI in AD may help understand the disease and monitor therapeutic responses in future clinical trials...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28552122/braim-a-computer-aided-diagnosis-system-for-neurodegenerative-diseases-and-brain-lesion-monitoring-from-volumetric-analyses
#19
Sandra Morales, Angela Bernabeu-Sanz, Fernando López-Mir, Pablo González, Luis Luna, Valery Naranjo
BACKGROUND AND OBJECTIVE: This paper presents BRAIM, a computer-aided diagnosis (CAD) system to help clinicians in diagnosing and treatment monitoring of brain diseases from magnetic resonance image processing. BRAIM can be used for early diagnosis of neurodegenerative diseases such as Parkinson, Alzheimer or Multiple Sclerosis and also for brain lesion diagnosis and monitoring. METHODS: The developed CAD system includes different user-friendly tools for segmenting and determining whole brain and brain structure volumes in an easy and accurate way...
July 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/28550283/high-resolution-bioelectrical-imaging-of-a%C3%AE-induced-network-dysfunction-on-cmos-meas-for-neurotoxicity-and-rescue-studies
#20
Hayder Amin, Thierry Nieus, Davide Lonardoni, Alessandro Maccione, Luca Berdondini
Neurotoxicity and the accumulation of extracellular amyloid-beta1-42 (Aβ) peptides are associated with the development of Alzheimer's disease (AD) and correlate with neuronal activity and network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is hampered by the paucity of reliable readouts and experimental models to study such functional decline from an early onset and to test rescue strategies within networks at cellular resolution. To overcome this important obstacle, we demonstrate a simple yet powerful in vitro AD model based on a rat hippocampal cell culture system that exploits large-scale neuronal recordings from 4096-electrodes on CMOS-chips for electrophysiological quantifications...
May 26, 2017: Scientific Reports
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