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https://www.readbyqxmd.com/read/28107493/white-matter-abnormalities-in-two-different-subtypes-of-amnestic-mild-cognitive-impairment
#1
Jianghong Liu, Peipeng Liang, Linlin Yin, Ni Shu, Tengda Zhao, Yi Xing, Fangyu Li, Zhilian Zhao, Kuncheng Li, Ying Han
White matter (WM) degeneration has been found during the course of cognitive decline in both Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), however, it is unclear whether there are different WM microstructural abnormalities between two subtypes of aMCI, including single domain aMCI (aMCI-s) and multiple domain aMCI (aMCI-m). Thirty-two patients of aMCI single-domain (aMCI-s), twenty-three patients of aMCI multiple-domain (aMCI-m) and twenty-three healthy normal controls (NC) participated in this study...
2017: PloS One
https://www.readbyqxmd.com/read/28107420/the-polyherbal-wattana-formula-displays-anti-amyloidogenic-properties-by-increasing-%C3%AE-secretase-activities
#2
Htut Htut Htoo, Suveerawan Limsuvan, Onusa Thamsermsang, Jean-François Hernandez, Frédéric Checler, Piyarat Govitrapong, Narawut Pakaprot, Pravit Akarasereenont, Bruno Vincent
Alzheimer's disease is characterized by the deposition of insoluble amyloid-β peptides produced from the β-amyloid precursor protein (βAPP). Because α-secretase cleavage by ADAM10 and ADAM17 takes place in the middle of Aβ, its activation is considered as a promising anti-AD therapeutic track. Here we establish that the polyherbal Wattana formula (WNF) stimulates sAPPα production in cells of neuronal and non-neuronal origins through an increase of both ADAM10 and ADAM17 catalytic activities with no modification of BACE1 activity and expression...
2017: PloS One
https://www.readbyqxmd.com/read/28107119/olfaction-new-understandings-diagnostic-applications
#3
Gabrielle F Ruggiero, Jeannette Y Wick
Estimates indicate that 14 million Americans have olfactory dysfunction. As with other senses, such as sight and hearing, olfaction frequently declines with age. Impaired olfaction can be a warning sign of Parkinson's disease, sometimes occurring before motor symptoms develop. It's also an initial symptom of Alzheimer's dementia (AD); the amyloid plaques and tangles characterizing AD invade the olfactory bulb and hippocampus early in its course, hampering odor identification. Olfactory dysfunction is associated with some serious problems, including inability to smell warning odors (fire, gas) and impaired ability to taste food...
November 1, 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28106992/discovery-of-n-pyridin-4-yl-1-5-naphthyridin-2-amines-as-potential-tau-pathology-pet-tracers-for-alzheimer-s-disease
#4
Frederik J R Rombouts, José-Ignacio Andrés, Manuela Ariza, José Manuel Alonso, Nigel Austin, Astrid Bottelbergs, Lu Chen, Vladimir Chupakhin, Erna Cleiren, Katleen Fierens, Alberto Fontana, Xavier Langlois, Joseph E Leenaerts, Jonas Mariën, Carolina Martinez Lamenca, Rhys Salter, Mark E Schmidt, Paula Te Riele, Cindy Wintmolders, Andrés A Trabanco, Wei Zhang, Gregor J Macdonald, Diederik Moechars
A mini-HTS on 4000 compounds selected using 2D fragment-based similarity and 3D pharmacophoric and shape similarity to known selective tau aggregate binders identified N-(6-methylpyridin-2-yl)quinolin-2-amine 10 as a novel potent binder to human AD aggregated tau with modest selectivity versus aggregated β-amyloid (Aβ). Initial medicinal chemistry efforts identified key elements for potency and selectivity, as well as suitable positions for radiofluorination, leading to a first generation of fluoroalkyl-substituted quinoline tau binding ligands with sub-optimal physicochemical properties...
January 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28106772/neuroprotective-and-anti-apoptotic-effects-of-csp-1103-in-primary-cortical-neurons-exposed-to-oxygen-and-glucose-deprivation
#5
Vanessa Porrini, Ilenia Sarnico, Marina Benarese, Caterina Branca, Mariana Mota, Annamaria Lanzillotta, Arianna Bellucci, Edoardo Parrella, Lara Faggi, Pierfranco Spano, Bruno Pietro Imbimbo, Marina Pizzi
CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer's disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impairment. Recent evidence suggests that CSP-1103 acts through a single molecular target, the amyloid precursor protein intracellular domain (AICD), a transcriptional regulator implicated in inflammation and apoptosis...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106563/comprehensive-screening-for-disease-risk-variants-in-early-onset-alzheimer-s-disease-genes-in-african-americans-identifies-novel-psen-variants
#6
Aurelie N'Songo, Minerva M Carrasquillo, Xue Wang, Thuy Nguyen, Yan Asmann, Steven G Younkin, Mariet Allen, Ranjan Duara, Maria T Greig Custo, Neill Graff-Radford, Nilüfer Ertekin-Taner
We conducted a comprehensive screening of rare coding variants in an African American cohort to identify novel pathogenic mutations within the early-onset Alzheimer's disease (EOAD) genes (APP, PSEN1, and PSEN2) in this understudied population. Whole-exome sequencing of 238 African American subjects identified 6 rare missense variants within the EOAD genes, which were observed in AD cases but never among controls. These variants were analyzed in an independent cohort of 300 African American subjects in which PSEN2:NM_000447:exon5:c...
January 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106562/plasma-amyloid-%C3%AE-peptides-in-type-2-diabetes-a-matched-case-control-study
#7
Kirsten E Peters, Wendy A Davis, Kevin Taddei, Ralph N Martins, Colin L Masters, Timothy M E Davis, David G Bruce
BACKGROUND: Plasma amyloid-β (Aβ) levels have rarely been investigated in type 2 diabetes despite its known associations with Alzheimer's disease. OBJECTIVE: To compare blood plasma Aβ concentrations (Aβ40 and Aβ42) in cognitively normal individuals with and without type 2 diabetes. METHODS: Plasma Aβ40 and Aβ42 were measured in 194 participants with diabetes recruited from the community-based Fremantle Diabetes Study Phase II cohort (mean age 71 years, 59% males) and 194 age-, sex-, and APOEɛ4 allele-matched, control subjects without diabetes from the Australian Imaging, Biomarkers and Lifestyle Study using a multiplex microsphere-based immunoassay...
January 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106561/the-modified-frontal-behavioral-inventory-fbi-mod-for-patients-with-frontotemporal-lobar-degeneration-alzheimer-s-disease-and-mild-cognitive-impairment
#8
Noora-Maria Suhonen, Ilona Hallikainen, Tuomo Hänninen, Jari Jokelainen, Johanna Krüger, Anette Hall, Maria Pikkarainen, Hilkka Soininen, Anne M Remes
While behavioral symptoms are both early and prevalent features of behavioral variant frontotemporal dementia (bvFTD), they can be present in other types of dementia as well, including Alzheimer's disease (AD) and even mild cognitive impairment (MCI). The Frontal Behavioral Inventory (FBI) was specifically developed to capture the behavioral and personality changes in bvFTD; it has also been modified into a self-administered caregiver questionnaire (FBI-mod). We examined the utility of the FBI-mod in differentiating bvFTD (n = 26), primary progressive aphasia (PPA) (n = 7), AD (n = 53), and MCI (n = 50) patients, and investigated how the FBI-mod may be associated with neuropsychological measures...
January 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106560/face-name-associative-recognition-deficits-in-subjective-cognitive-decline-and-mild-cognitive-impairment
#9
Alexandra Polcher, Ingo Frommann, Alexander Koppara, Steffen Wolfsgruber, Frank Jessen, Michael Wagner
BACKGROUND: There is a need for more sensitive neuropsychological tests to detect subtle cognitive deficits emerging in the preclinical stage of Alzheimer's disease (AD). Associative memory is a cognitive function supported by the hippocampus and affected early in the process of AD. OBJECTIVE: We developed a short computerized face-name-associative-recognition test (FNART) and tested whether it would detect memory impairment in memory-clinic patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD)...
January 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106559/abca1-deficiency-affects-basal-cognitive-deficits-and-dendritic-density-in-mice
#10
Nicholas F Fitz, Alexis Y Carter, Victor Tapias, Emilie L Castranio, Ravindra Kodali, Iliya Lefterov, Radosveta Koldamova
ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins and regulates the generation of high density lipoproteins. Previously, we have shown that lack of Abca1 significantly increases amyloid deposition and cognitive deficits in Alzheimer's disease model mice expressing human amyloid-β protein precursor (APP). The goal of this study was to determine if ABCA1 plays a role in memory deficits caused by amyloid-β (Aβ) oligomers and examine neurite architecture of pyramidal hippocampal neurons...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106558/validation-of-suspected-somatic-single-nucleotide-variations-in-the-brain-of-alzheimer-s-disease-patients
#11
Alberto Gomez-Ramos, Angel J Picher, Esther García, Patricia Garrido, Felix Hernandez, Eduardo Soriano, Jesús Avila
Next-generation sequencing techniques and genome-wide association study analyses have provided a huge amount of data, thereby enabling the identification of DNA variations and mutations related to disease pathogenesis. New techniques and software tools have been developed to improve the accuracy and reliability of this identification. Most of these tools have been designed to discover and validate single nucleotide variants (SNVs). However, in addition to germ-line mutations, human tissues bear genomic mosaicism, which implies that somatic events are present only in low percentages of cells within a given tissue, thereby hindering the validation of these variations using standard genetic tools...
January 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106557/blunted-respiratory-responses-in%C3%A2-the%C3%A2-streptozotocin-induced-alzheimer-s-disease-rat-model
#12
Dalton L Ebel, Christopher G Torkilsen, Tim D Ostrowski
Alzheimer's disease (AD) is known for the progressive decline of cognition and memory. In addition to these disease-defining symptoms, impairment of respiratory function is frequently observed and often expressed by sleep-disordered breathing or reduced ability to adjust respiration when oxygen demand is elevated. The mechanisms for this are widely unknown. Postmortem analysis from the brainstem of AD patients reveals pathological alterations, including in nuclei responsible for respiratory control. In this study, we analyzed respiratory responses and morphological changes in brainstem nuclei following intracerebroventricular (ICV) injections of streptozotocin (STZ), a rat model commonly used to mimic sporadic AD...
January 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106556/an-improved-drugs-screening-system-reveals-that-baicalein-ameliorates-the-a%C3%AE-ampa-nmda-induced-depolarization-of-neurons
#13
Tian-Syuan Lin, Han-Jung Tsai, Chih-Han Lee, Yan-Qing Song, Rih-Sheng Huang, Hsiu-Mei Hsieh-Li, Mei-Chih Liang, Yenshou Lin
The presence of amyloid-β (Aβ) plaque and tau protein hyperphosphorylation in brain tissue is the pathological hallmark of Alzheimer's disease (AD). At least some Aβ neurotoxicity is caused by the presence of excess glutamate that has been induced by Aβ accumulation. Memantine is currently the only NMDA receptor inhibitor approved for treating moderate-to-severe AD patients. We utilized primary cortical neurons and DiBAC4(3), a slow-response voltage sensitive fluorescence dye, to create a novel system for screening herbal medicines that allows the identification of pure compounds able to ameliorate Aβ-induced abnormal depolarization...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106555/optical-coherence-tomography-reveals-retinal-neuroaxonal-thinning-in-frontotemporal-dementia-as-in-alzheimer-s-disease
#14
Laura Ferrari, Su-Chun Huang, Giuseppe Magnani, Alessandro Ambrosi, Giancarlo Comi, Letizia Leocani
BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are leading causes of cognitive decline. Optical coherence tomography (OCT) allows the measurement of thickness of retinal neuroaxonal layers. While in AD and mild cognitive impairment (MCI), retinal nerve fiber layer (RNFL) thinning is frequently reported, less information is available on ganglion cell layer-inner plexiform layer (GCL-IPL). Data on FTD are lacking. OBJECTIVE: To obtain cross-sectional information on RNFL and GCL-IPL thickness among MCI, AD, FTD, and healthy controls (HC), and their correlations with dementia severity...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106554/recovery-from-proactive-semantic-interference-in-mild-cognitive-impairment-and-normal-aging-relationship-to-atrophy-in-brain-regions-vulnerable-to-alzheimer-s-disease
#15
David A Loewenstein, Rosie E Curiel, Clinton Wright, Xiaoyan Sun, Noam Alperin, Elzabeth Crocco, Sara J Czaja, Arlene Raffo, Ailyn Penate, Jose Melo, Kimberly Capp, Monica Gamez, Ranjan Duara
BACKGROUND: There is growing evidence that proactive semantic interference (PSI) and failure to recover from PSI may represent early features of Alzheimer's disease (AD). OBJECTIVE: This study investigated the association between PSI, recovery from PSI, and reduced MRI volumes in AD signature regions among cognitively impaired and unimpaired older adults. METHODS: Performance on the LASSI-L (a novel test of PSI and recovery from PSI) and regional brain volumetric measures were compared between 38 cognitively normal (CN) elders and 29 older participants with amnestic mild cognitive impairment (MCI)...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106552/meditation-and-music-improve-memory-and-cognitive-function-in-adults-with-subjective-cognitive-decline-a-pilot-randomized-controlled-trial
#16
Kim E Innes, Terry Kit Selfe, Dharma Singh Khalsa, Sahiti Kandati
BACKGROUND: While effective therapies for preventing or slowing cognitive decline in at-risk populations remain elusive, evidence suggests mind-body interventions may hold promise. OBJECTIVES: In this study, we assessed the effects of Kirtan Kriya meditation (KK) and music listening (ML) on cognitive outcomes in adults experiencing subjective cognitive decline (SCD), a strong predictor of Alzheimer's disease. METHODS: Sixty participants with SCD were randomized to a KK or ML program and asked to practice 12 minutes/day for 3 months, then at their discretion for the ensuing 3 months...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106551/conscientiousness-is-negatively-associated-with-grey-matter-volume-in-young-apoe%C3%A9-4-carriers
#17
Lukas Kunz, Martin Reuter, Nikolai Axmacher, Christian Montag
The etiology of late onset Alzheimer's disease (LOAD) depends on multiple factors, among which the APOEɛ4 allele is the most adverse genetic determinant and conscientiousness represents an influential personality trait. A potential association of both factors with brain structure in young adulthood may constitute a constellation that sets the course toward or against the subtle disease progression of LOAD that starts decades before clinical manifestation. Hence, in the present study, we examined the modulating effects of APOEɛ4 on the relation between personality dimensions, including conscientiousness, and total grey matter volume (GMV) in young healthy adults using an a priori genotyping design...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106548/does-the-female-advantage-in-verbal-memory-contribute-to-underestimating-alzheimer-s-disease-pathology-in-women-versus-men
#18
Erin E Sundermann, Anat Biegon, Leah H Rubin, Richard B Lipton, Susan Landau, Pauline M Maki
There is a growing recognition of sex differences in Alzheimer's disease (AD). Females show an advantage over males on tests of verbal memory, which are used to diagnose AD and its precursor, amnestic mild cognitive impairment (aMCI). Women retain this advantage in aMCI despite reduced hippocampal volume and temporal lobe glucose metabolism. Here we examined whether this female advantage endures despite evidence of AD-specific pathology, cortical amyloid-β (Aβ) deposition measured with [18F]AV45 (florbetapir) positron emission tomography...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106546/a-common-variant-of-il-6r-is-associated-with-elevated-il-6-pathway-activity-in-alzheimer-s-disease-brains
#19
Patrick C G Haddick, Jessica L Larson, Nisha Rathore, Tushar R Bhangale, Qui T Phung, Karpagam Srinivasan, David V Hansen, Jennie R Lill, Margaret A Pericak-Vance, Jonathan Haines, Lindsay A Farrer, John S Kauwe, Gerard D Schellenberg, Carlos Cruchaga, Alison M Goate, Timothy W Behrens, Ryan J Watts, Robert R Graham, Joshua S Kaminker, Marcel van der Brug
The common p.D358A variant (rs2228145) in IL-6R is associated with risk for multiple diseases and with increased levels of soluble IL-6R in the periphery and central nervous system (CNS). Here, we show that the p.D358A allele leads to increased proteolysis of membrane bound IL-6R and demonstrate that IL-6R peptides with A358 are more susceptible to cleavage by ADAM10 and ADAM17. IL-6 responsive genes were identified in primary astrocytes and microglia and an IL-6 gene signature was increased in the CNS of late onset Alzheimer's disease subjects in an IL6R allele dependent manner...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106153/altered-motion-repulsion-in-alzheimer-s-disease
#20
Yan Li, Shougang Guo, Yongxiang Wang, Huan Chen
Recent research in Alzheimer's disease (AD) indicates that perceptual impairments may occur before the onset of cognitive declines, and can thus serve as an early noninvasive indicator for AD. In this study, we focused on visual motion processing and explored whether AD induces changes in the properties of direction repulsion between two competing motions. We used random dot kinematograms (RDKs) and measured the magnitudes of direction repulsion between two overlapping RDKs moving different directions in three groups of participants: an AD group, an age-matched old control group, and a young control group...
January 20, 2017: Scientific Reports
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