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Familial Alzheimer's disease

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https://www.readbyqxmd.com/read/28922152/brain-biomarkers-in-familial-alzheimer-s-disease-mouse-models
#1
Yafit Kuttner-Hirshler, Palamadai N Venkatasubramanian, Joan Apolinario, Jacqueline Bonds, Alice M Wyrwicz, Orly Lazarov
Alzheimer's disease (AD) is characterized by progressive loss of memory and cognitive deterioration. It is thought that the onset of the disease takes place several decades before memory deficits are apparent. Reliable biomarkers for the diagnosis or prognostication of the disease are highly desirable. Neural stem cells (NSC) exist in the adult brain throughout life and give rise to neural progenitor cells (NPC), which differentiate into neurons or glia. The level of NPC proliferation and new neuron formation is significantly compromised in mouse models of familial Alzheimer's disease (FAD)...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28919280/soluble-gamma-secretase-modulators-attenuate-alzheimer-s-%C3%AE-amyloid-pathology-and-induce-conformational-changes-in-presenilin-1
#2
Frank Raven, Joseph F Ward, Katarzyna M Zoltowska, Yu Wan, Enjana Bylykbashi, Sean J Miller, Xunuo Shen, Se Hoon Choi, Kevin D Rynearson, Oksana Berezovska, Steven L Wagner, Rudolph E Tanzi, Can Zhang
A central pathogenic event of Alzheimer's disease (AD) is the accumulation of the Aβ42 peptide, which is generated from amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. We have developed a class of soluble 2-aminothiazole γ-secretase modulators (SGSMs) that preferentially decreases Aβ42 levels. However, the effects of SGSMs in AD animals and cells expressing familial AD mutations, as well as the mechanism of γ-secretase modulation remain largely unknown. Here, a representative of this SGSM scaffold, SGSM-36, was investigated using animals and cells expressing FAD mutations...
September 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28917837/memantine-inhibits-%C3%AE-amyloid-aggregation-and-disassembles-preformed-%C3%AE-amyloid-aggregates
#3
Kaori Ito, Mitsuhiro Makino, Keiko Okado, Taisuke Tomita
Memantine, an uncompetitive glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, is widely used as a medication for the treatment of Alzheimer's disease (AD). We previously reported that chronic treatment of AD with memantine reduces the amount of insoluble β-amyloid (Aβ) and soluble Aβ oligomers in animal models of AD. The mechanisms by which memantine reduces Aβ levels in the brain were evaluated by determining the effect of memantine on Aβ aggregation using thioflavin T and transmission electron microscopy...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28914991/resistiveness-to-care-as-experienced-by-family-caregivers-providing-care-for-someone-with-dementia
#4
Pamela C Spigelmyer, Judith E Hupcey, Carol A Smith, Susan J Loeb, Lisa Kitko
PURPOSE: This research explored family caregivers' lived experiences of resistiveness to care when they provided care for people with dementia. The goal was to identify a general meaning of family caregivers' lived experiences to target potential areas for future nursing interventions to help family caregivers manage their caregiving role and provide a base for future research surrounding resistiveness to care. DESIGN: Descriptive phenomenology was used to provide descriptions of eight family caregivers who provided care for someone with dementia and experienced resistiveness to care...
September 15, 2017: Journal of Nursing Scholarship
https://www.readbyqxmd.com/read/28914221/-the-default-setting-of-memory-is-forgetting
#5
D Draaisma
From the age of about 60, many people begin to experience difficulties with tasks that require the use of prospective memory and begin to have trouble finding words and names. Worried that these symptoms may be indicative of the onset of Alzheimer's disease, many of them fill in online self-tests or consult their family doctor. In the vast majority of cases, symptoms like these indicate completely natural age-related forgetfulness. Physicians should encourage a socially active lifestyle to slow down further decline...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28912154/inhibition-of-p25-cdk5-attenuates-tauopathy-in-mouse-and-ipsc-models-of-frontotemporal-dementia
#6
Jinsoo Seo, Oleg Kritskiy, L Ashley Watson, Scarlett J Barker, Dilip Dey, Waseem K Raja, Yuan-Ta Lin, Tak Ko, Sukhee Cho, Jay Penney, M Catarina Silva, Steven D Sheridan, Diane Lucente, James F Gusella, Bradford C Dickerson, Stephen J Haggarty, Li-Huei Tsai
Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cyclin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders including Alzheimer's disease (AD). Previously, we showed that replacing endogenous p35 with the non-cleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial AD mouse model. Here, to address the role of p25/Cdk5 in tauopathy, we generated double transgenic mice by crossing mice overexpressing mutant human tau (P301S) with Δp35KI mice...
September 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28911974/molecular-genetics-of-the-transcription-factor-glis3-identifies-its-dual-function-in-beta-cells-and-neurons
#7
Sophie Calderari, Massimiliano Ria, Christelle Gérard, Tatiane C Nogueira, Olatz Villate, Stephan C Collins, Helen Neil, Nicolas Gervasi, Christophe Hue, Nicolas Suarez-Zamorano, Cécilia Prado, Miriam Cnop, Marie-Thérèse Bihoreau, Pamela J Kaisaki, Jean-Baptiste Cazier, Cécile Julier, Mark Lathrop, Michel Werner, Decio L Eizirik, Dominique Gauguier
The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q<0.05; enrichment range 1.40-9.11 fold) sharing the motif wrGTTCCCArTAGs, which were enriched in genes involved in neuronal function and autophagy and in risk genes for metabolic and neuro-behavioural diseases. We confirmed experimentally Glis3-mediated regulation of the expression of genes involved in autophagy and neuron function in INS1 and neuronal PC12 cells...
September 11, 2017: Genomics
https://www.readbyqxmd.com/read/28904001/kv3-channels-enablers-of-rapid-firing-neurotransmitter-release-and-neuronal-endurance
#8
REVIEW
Leonard K Kaczmarek, Yalan Zhang
The intrinsic electrical characteristics of different types of neurons are shaped by the K(+) channels they express. From among the more than 70 different K(+) channel genes expressed in neurons, Kv3 family voltage-dependent K(+) channels are uniquely associated with the ability of certain neurons to fire action potentials and to release neurotransmitter at high rates of up to 1,000 Hz. In general, the four Kv3 channels Kv3.1-Kv3.4 share the property of activating and deactivating rapidly at potentials more positive than other channels...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28898051/effect-of-alzheimer-familial-chromosomal-mutations-on-the-amyloid-fibril-interaction-with-different-pet-tracers-insight-from-molecular-modeling-studies
#9
Kanagasabai Balamurugan, Natarajan Arul Murugan, Bengt Långström, Agneta Nordberg, Hans Ågren
Alzheimer's disease (AD) is the most common neurodegenerative disorder. Along with an increasing number of elderly worldwide it poses a great challenge for the society and healthcare. Although sporadic AD is the common form of AD, 2-3% of the AD cases are expected to be due to mutations in the beta region of the amyloid precursor protein which is referred to as autosomal dominant AD (ADAD). These mutations may cause changes in the secondary structure of the amyloid beta fibrils and may alter the fibrillization rate leading to changes in the disease development and could also affect the binding to tracers used in diagnosis...
September 12, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28890319/arctic-a%C3%AE-40-blocks-the-nicotine-induced-neuroprotective-effect-of-chrna7-by-inhibiting-the-erk1-2-pathway-in-human-neuroblastoma-cells
#10
Ye Ju, Toru Asahi, Naoya Sawamura
Amyloid β protein (Aβ) plays a central role in Alzheimer's disease (AD) pathogenesis. Point mutations in the Aβ sequence, which cluster around the central hydrophobic core of the peptide, are associated with familial AD (FAD). Several mutations have been identified, with the Arctic mutation exhibiting a purely cognitive phenotype that is typical of AD. Our previous findings suggest that Arctic Aβ40 binds to and aggregates with CHRNA7, thereby inhibiting the calcium response and signaling pathways downstream of the receptor...
September 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28888721/tmem106b-and-apoe-polymorphisms-in-chmp2b-mediated-frontotemporal-dementia-ftd-3
#11
Nina Rostgaard, Peter Roos, Esben Budtz-Jørgensen, Peter Johannsen, Gunhild Waldemar, Anne Nørremølle, Suzanne G Lindquist, Susanne Gydesen, Jeremy M Brown, John Collinge, Adrian M Isaacs, Troels T Nielsen, Jørgen E Nielsen
Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset (AAO) and progression in terms of age at institutionalization (AAI) and age at death (AAD)...
July 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28888073/selective-decline-of-neurotrophin-and-neurotrophin-receptor-genes-within-ca1-pyramidal-neurons-and-hippocampus-proper-correlation-with-cognitive-performance-and-neuropathology-in-mild-cognitive-impairment-and-alzheimer-s-disease
#12
Stephen D Ginsberg, Michael H Malek-Ahmadi, Melissa J Alldred, Shaoli Che, Irina Elarova, Yinghua Chen, Freddy Jeanneteau, Thorsten M Kranz, Moses V Chao, Scott E Counts, Elliott J Mufson
Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom-designed microarray analysis, and qPCR of CA1 subregional dissections...
September 9, 2017: Hippocampus
https://www.readbyqxmd.com/read/28887919/cassia-tora-linn-a-boon-to-alzheimer-s-disease-for-its-anti-amyloidogenic-and-cholinergic-activities
#13
K R Chethana, Fatma Sezer Senol, Ilkay Erdogan Orhan, K R Anilakumar, Rangappa S Keri
BACKGROUND: Drug discovery from natural products as alternatives for Alzheimer's disease (AD) is a current trend. For which plant is an alternative for searching potential molecule for treating AD. Availability of Cassia tora as weed and abundance in nature makes it as potential source. Many plants group under Leguminosae family has potential medicinal property of which Cassia tora is an appropriate choice, to know potency against AD. Etiology of AD is described by senile plaques and neurofibrillary tangles...
September 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28879407/microrna-profiling-in-aging-brain-of-psen1-psen2-double-knockout-mice
#14
Suji Ham, Tae Kyoo Kim, Sangjoon Lee, Ya-Ping Tang, Heh-In Im
MicroRNAs are small non-coding RNAs that function as regulators of gene expression. The altered expression of microRNAs influences the pathogenesis of Alzheimer's disease. Many researchers have focused on studies based on the relatively distinctive etiology of familial Alzheimer's disease due to the absence of risk factors in the pathogenesis of sporadic Alzheimer's disease. Although there is a limitation in Alzheimer's disease studies, both Alzheimer's disease types have a common risk factor-aging. No study to date has examined the aging factor in Alzheimer's disease animal models with microRNAs...
September 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28877271/spinal-cord-homogenates-from-sod1-familial-amyotrophic-lateral-sclerosis-induce-sod1-aggregation-in-living-cells
#15
Edward Pokrishevsky, Ran Ha Hong, Ian R Mackenzie, Neil R Cashman
Mutant Cu/Zn superoxide dismutase (SOD1) can confer its misfolding on wild-type SOD1 in living cells; the propagation of misfolding can also be transmitted between cells in vitro. Recent studies identified fluorescently-tagged SOD1G85R as a promiscuous substrate that is highly prone to aggregate by a variety of templates, in vitro and in vivo. Here, we utilized several SOD1-GFP reporter proteins with G37R, G85R, or G93A mutations in SOD1. We observed that human spinal cord homogenates prepared from SOD1 familial ALS (FALS) can induce significantly more intracellular reporter protein aggregation than spinal cord homogenates from sporadic ALS, Alzheimer's disease, multiple system atrophy or healthy control individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28870815/activation-of-transient-receptor-potential-melastatin-7-trpm7-channel-increases-basal-autophagy-and-reduces-amyloid-%C3%AE-peptide
#16
Hyun Geun Oh, Sungkwon Chung
Cerebral accumulation of amyloid β-peptide (Aβ), which is produced from amyloid precursor protein (APP), is the primary cause of Alzheimer's disease (AD). Autophagy recycles cellular components and digests intracellular components including Aβ. The Ca(2+)- and Mg(2+)-permeable transient receptor potential melastatin 7 (TRPM7) channel underlies the constitutive Ca(2+) influx in some cells. Since we already reported that TRPM7 channel-mediated Ca(2+) influx regulates basal autophagy, we hypothesize that the activation of TRPM7 channel could increase basal autophagy and consequently decrease Aβ...
September 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28870521/clinical-aspects-and-biomarkers-of-alzheimer-s-disease-in-down-syndrome
#17
REVIEW
Panagiotis Zis, Andre Strydom
Alzheimer's disease (AD) may affect in excess of 90% of individuals with Down syndrome (DS) after age 60, due to duplication of the APP gene in trisomy of chromosome 21, with neuropathology that is comparable to Sporadic AD and Familial AD (FAD). Previous literature suggested some unique features in clinical presentation of dementia in DS (DSd), which might be due to diagnostic difficulties, or represent a real difference compared to SAD or FAD. We review current knowledge on clinical diagnosis and presentation of dementia in DS in comparison with FAD due to APP mutations and APP duplication...
September 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28869657/self-reported-personality-traits-are-prospectively-associated-with-proxy-reported-behavioral-and-psychological-symptoms-of-dementia-at-the-end-of-life
#18
Angelina R Sutin, Yannick Stephan, Martina Luchetti, Antonio Terracciano
OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) are among the most challenging aspects of Alzheimer disease for patients and their families. Previous studies have found associations between informant-reported retrospective personality and BPSD; we test whether prospective, self-reported personality predicts who will experience these symptoms. METHODS: Deceased participants from the Health and Retirement Study who had evidence of cognitive impairment at the end of life (N = 1988) were selected to examine whether self-reported five-factor model personality traits, measured up to 8 years before death, were associated with proxy-reported BPSD...
September 4, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28869463/risk-factors-neuroanatomical-correlates-and-outcome-of-neuropsychiatric-symptoms-of-alzheimer-s-disease
#19
Stéphane P Poulin, David Bergeron, Bradford C Dickerson
BACKGROUND: An integrative model of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) is lacking. OBJECTIVE: In this study, we aimed to investigate the risk factors, anatomy, biology, and outcomes of NPS in AD. METHODS: 181 subjects were included from the Alzheimer's Disease Neuroimaging Study (ADNI). NPS were assessed with the Neuropsychiatric Inventory Questionnaire at baseline and 6 months. NPI >3 was used as a threshold for NPS positivity...
September 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28858144/exploring-an-unknown-territory-sleeping-beauties-in-the-nursing-research-literature
#20
Peter Kokol, Helena Blažun Vošner, Joeri Vermeulen
BACKGROUND: Sleeping Beauties (SBs) are publications that are scarcely cited in the years immediately following publication but then suddenly become highly cited later. Such publications have unique citation patterns and can reveal important developments in the field in which they appear. OBJECTIVES: No holistic analysis of nursing SBs has been done yet. The aim of this study was to identify and analyze the SB phenomenon in the nursing research literature. METHOD: The corpus for the nursing SB identification was harvested from the Web of Science Core Collection (Thomas Reuters) for the period 1934-2015...
September 2017: Nursing Research
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