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Familial Alzheimer's disease

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https://www.readbyqxmd.com/read/28544981/synthesis-and-in%C3%A2-vitro-evaluation-of-new-fluorinated-quinoline-derivatives-with-high-affinity-for-pde5-towards-the-development-of-new-pet-neuroimaging-probes
#1
Jianrong Liu, Aurélie Maisonial-Besset, Barbara Wenzel, Damien Canitrot, Ariane Baufond, Jean-Michel Chezal, Peter Brust, Emmanuel Moreau
The increasing incidence of Alzheimer's disease (AD) worldwide is a major public health problem. Current treatments provide only palliative solutions with significant side effects. Therefore, new efficient treatment options and novel early diagnosis tools are urgently needed. Recently, strong pre-clinical evidences suggested that phosphodiesterase 5 (PDE5) may be clinically relevant both as biomarker and drug-target in AD. In this study, we intended to develop a new radiofluorinated tracer for the visualisation of PDE5 in brain using PET imaging...
April 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28542120/deaths-from-alzheimer-s-disease-united-states-1999-2014
#2
Christopher A Taylor, Sujay F Greenlund, Lisa C McGuire, Hua Lu, Janet B Croft
Alzheimer's disease (Alzheimer's), an ultimately fatal form of dementia, is the sixth leading cause of death in the United States, accounting for 3.6% of all deaths in 2014 (1,2). Alzheimer's deaths can be an indicator of paid and unpaid caregiver burden because nearly everyone in the final stages of Alzheimer's needs constant care, regardless of the setting, as the result of functional and cognitive declines (2). To examine deaths with Alzheimer's as the underlying cause, state-level and county-level death certificate data from the National Vital Statistics System for the period 1999-2014 were analyzed...
May 26, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28540926/entorhinal-cortical-deep-brain-stimulation-rescues-memory-deficits-in-both-young-and-old-mice-genetically-engineered-to-model-alzheimer-s-disease
#3
Frances Xia, Adelaide Yiu, Scellig Sd Stone, Soojin Oh, Andres M Lozano, Sheena A Josselyn, Paul W Frankland
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Deep brain stimulation (DBS) has been used to treat a variety of brain disorders and shows promise in alleviating cognitive symptoms in some AD patients (Laxton et al., 2010). We previously showed that DBS of the entorhinal cortex (EC) enhances spatial memory formation in normal (wild-type) mice (Stone et al., 2011). Here we tested the effects of EC-DBS on the progressive cognitive deficits in a genetically-based mouse model of AD...
May 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28540771/identifying-therapeutic-targets-for-alzheimer-s-disease-with-big-data
#4
Nilüfer Ertekin-Taner
Nilüfer Ertekin-Taner is a Professor of Neuroscience and Neurology at the Mayo Clinic, Jacksonville, FL, USA. A neurogeneticist and board-certified behavioral neurologist, she received her medical degree from Hacettepe University Medical School in Ankara, Turkey and her doctorate degree in Molecular Neuroscience from Mayo Graduate School. She completed her residency training in the Department of Neurology at Mayo Clinic in Rochester (MN, USA) and fellowship in Behavioral Neurology at Mayo Clinic in Jacksonville...
April 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/28538697/mammalian-metallothionein-3-new-functional-and-structural-insights
#5
REVIEW
Milan Vašák, Gabriele Meloni
Metallothionein-3 (MT-3), a member of the mammalian metallothionein (MT) family, is mainly expressed in the central nervous system (CNS). MT-3 possesses a unique neuronal growth inhibitory activity, and the levels of this intra- and extracellularly occurring metalloprotein are markedly diminished in the brain of patients affected by a number of metal-linked neurodegenerative disorders, including Alzheimer's disease (AD). In these pathologies, the redox cycling of copper, accompanied by the production of reactive oxygen species (ROS), plays a key role in the neuronal toxicity...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28537903/amyloid-precursor-like-protein-1-promotes-jnk-mediated-cell-migration-in-drosophila
#6
Xingjun Wang, Ying Sun, Shilong Han, Chenxi Wu, Yeqing Ma, Yu Zhao, Yingyao Shao, Yujun Chen, Lingzhi Kong, Wenzhe Li, Fan Zhang, Lei Xue
The amyloid precursor like protein-1 (APLP1) is a member of the amyloid precursor protein (APP) family in mammals. While many studies have been focused on the pathologic role of APP in Alzheimer's disease, the physiological functions of APLP1 have remained largely elusive. Here we report that ectopic expression of APLP1 in Drosophila induces cell migration, which is suppressed by the loss of JNK signaling and enhanced by the gain of JNK signaling. APLP1 activates JNK signaling through phosphorylation of JNK, which up-regulates the expression of matrix metalloproteinase MMP1 required for basement membranes degradation and promotes actin remodeling essential for cell migration...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534696/light-sleep-and-circadian-rhythms-in-older-adults-with-alzheimer-s-disease-and-related-dementias
#7
Mariana G Figueiro
Alzheimer's disease and related dementias (ADRD) can cause sleep and behavioral problems that are problematic for ADRD patients and their family caregivers. Light therapy has shown promise as a nonpharmacological treatment, and preliminary studies demonstrate that timed light exposure can consolidate and improve nighttime sleep efficiency, increase daytime wakefulness and reduce evening agitation without the adverse effects of pharmacological solutions. Compliance with light treatment and the accurate measurement of light exposures during treatment, however, have presented barriers for the adoption of light therapy for ADRD...
May 23, 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/28533041/-alzheimer-s-disease-and-training-for-carers-in-a-rural-region
#8
Marie-Laure Lecat, Frank Pizon, Cédric Kempf
Alzheimer's disease or related diseases constitute a major public health issue at the heart of the 2014-2019 plan for neurodegenerative diseases. Family carers, seeing to the day-to-day care of their loved ones, require support, particularly in rural regions. A study carried out of these carers sought to understand their perception of Alzheimer's disease, their role, and in what ways their training can help to reduce their physical and mental exhaustion in order to improve their quality of life.
May 2017: Soins. Gérontologie
https://www.readbyqxmd.com/read/28532646/the-novel-psen1-m84v-mutation-associated-to-frontal-dysexecutive-syndrome-spastic-paraparesis-and-cerebellar-atrophy-in-a-dominant-alzheimer-s-disease-family
#9
Maura Gallo, Francesca Frangipane, Chiara Cupidi, Matteo De Bartolo, Sabina Turone, Camilla Ferrari, Benedetta Nacmias, Giuliana Grimaldi, Valentina Laganà, Rosanna Colao, Livia Bernardi, Maria Anfossi, Maria Elena Conidi, Franca Vasso, Sabrina Anna Maria Curcio, Maria Mirabelli, Nicoletta Smirne, Giusi Torchia, Maria Gabriella Muraca, Gianfranco Puccio, Raffaele Di Lorenzo, Maristella Piccininni, Andrea Tedde, Raffaele Giovanni Maletta, Sandro Sorbi, Amalia Cecilia Bruni
We identified the novel PSEN1 pathogenic mutation M84V in 3 patients belonging to a large kindred affected by autosomal dominant Alzheimer's disease (AD). The clinical phenotype was characterized by early onset dementia in 14 affected subjects over 3 generations. Detailed clinical, imaging and genetic assessment was performed. We highlighted the presence of unusual symptoms such as frontal executive syndrome, psychosis and spastic paraparesis in these patients. Spastic paraparesis has been reported in other PSEN1 mutations in adjacent codons, suggesting that the position of the genetic defect may affect the clinical expression, although this phenotype can occur in mutations throughout the whole PSEN1 gene...
April 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28532645/identification-of-a-novel-psen1-mutation-leu232pro-in-a-korean-patient-with-early-onset-alzheimer-s-disease-and-a-family-history-of-dementia
#10
Jiyun Park, Seong Soo A An, Vo Van Giau, Kyuhwan Shim, Young Chul Youn, Eva Bagyinszky, SangYun Kim
In the present study, a novel mutation in exon 7 of presenilin 1 (Leu232Pro) was discovered in a Korean patient with early-onset Alzheimer's disease, who represented memory decline at 37 years of age, followed by impairment in spatial activity and concentrations and personality changes. Imaging analyses with magnetic resonance scan showed diffuse atrophy in the frontoparietal regions. Targeted next generation sequencing and Sanger sequencing identified a heterozygous T to C transition at position 695 (c.695T>C) of in presenilin 1 gene (PSEN1), resulting in a novel missense mutation at codon 232 from leucine to proline (L232P)...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28531378/cognitive-ability-in-young-adulthood-and-risk-of-dementia-in-a-cohort-of-danish-men-brothers-and-twins
#11
Merete Osler, Gunhild T Christensen, Ellen Garde, Erik L Mortensen, Kaare Christensen
INTRODUCTION: We examined the association between cognitive ability in young adulthood and dementia in Danish men, brothers, and male twins. METHODS: In total, 666,986 men born between 1939 and 1959 were identified for dementia diagnosis in national registries from 1969 to 2016. The association between cognitive ability from draft board examination and dementia was examined using Cox regression. RESULTS: During a 44-year follow-up, 6416 (0...
May 19, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28530016/assessment-of-caregiving-constructs-toward-a-personal-familial-group-and-cultural-construction-of-dementia-care-through-the-eyes-of-personal-construct-psychology
#12
Eradah O Hamad, Ahmad N AlHadi, Christopher J Lee, Marie Y Savundranayagam, Jeffrey D Holmes, Elizabeth Anne Kinsella, Andrew M Johnson
Conditions that cause cognitive impairment and behavioural and personality changes, such as Alzheimer's disease (AD) and related dementia, have global impact across cultures. However, the experience of dementia care can vary between individuals, families, formal caregivers, and social groups from various cultures. Self-reported measures, caregiving stress models, and conceptual theories have been developed to address the physical, financial, psychological, and social factors associated with the experience of dementia care...
May 22, 2017: Journal of Cross-cultural Gerontology
https://www.readbyqxmd.com/read/28528968/amylin-and-its-g-protein-coupled-receptor-a-probable-pathological-process-and-drug-target-for-alzheimer-s-disease
#13
REVIEW
Wei Qiao Qiu
G-protein-coupled receptors (GPCRs) are shown to be involved in Alzheimer's disease (AD) pathogenesis. However, because GPCRs include a large family of membrane receptors, it is unclear which specific GPCR or pathway with rational ligands can become effective therapeutic targets for AD. Amylin receptor (AmR) is a GPCR that mediates several activities, such as improving glucose metabolism, relaxing cerebrovascular structure, modulating inflammatory reactions and potentially enhancing neural regeneration. Recent studies show that peripheral treatments with amylin or its clinical analog, pramlintide, reduced several components of AD pathology, including amyloid plaques, tauopathy, neuroinflammation and other components in the brain, corresponding with improved learning and memory in AD mouse models...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28523554/alzheimer-s-disease-and-histone-code-alterations
#14
Pritika Narayan, Mike Dragunow
Substantial progress has been made in identifying Alzheimer's disease (AD) risk-associated variants using genome-wide association studies (GWAS). The majority of these risk variants reside in noncoding regions of the genome making their functional evaluation difficult; however, they also infer the presence of unconventional regulatory regions that may reside at these locations. We know from these studies that rare familial cases of AD account for less than 5% of all AD cases and autosomal dominant mutations in APP, PSEN1 and PSEN2 account for less than 10% of the genetic basis of these familial cases [1]...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#15
Anna Wilkaniec, Magdalena Gąssowska, Grzegorz A Czapski, Magdalena Cieślik, Grzegorz Sulkowski, Agata Adamczyk
Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy bodies, Alzheimer's disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling-particularly, P2 family receptors-in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied...
May 17, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28514669/the-relationship-between-cognition-and-depressive-symptoms-and-factors-modifying-this-association-in-alzheimer-s-disease-a-multivariate-multilevel-model
#16
Bei Yang, Hongmei Yu, Min Xing, Runlian He, Ruifeng Liang, Liye Zhou
OBJECTIVES: To examine whether there was a bidirectional association between cognition and depressive symptoms in Alzheimer's disease (AD), and to explore the role of socio-demographic factors and daily performance in this association. METHODS: We conducted a longitudinal study of 104 community-dwelling patients with confirmed AD from Taiyuan, China. We assessed cognition and depressive symptoms (dependent variables) with the Montreal Cognitive Assessment (MoCA) and the Geriatric Depression Scale-30 (GDS-30), respectively...
May 10, 2017: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/28506438/prion-like-spreading-in-tauopathies
#17
REVIEW
Jacob I Ayers, Benoit I Giasson, David R Borchelt
Tau is a microtubule-associated protein that functions in regulating cytoskeleton dynamics, especially in neurons. Misfolded and aggregated forms of tau produce pathological structures in a number of neurodegenerative diseases, including Alzheimer's disease (AD) and tauopathy dementias. These disorders can present with a sporadic etiology, such as in AD, or a familial etiology, such as in some cases of frontotemporal dementia with parkinsonism. Notably, the pathological features of tau pathology in these diseases can be very distinct...
April 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28504912/synthesis-and-biological-assessment-of-racemic-benzochromenopyrimidinetriones-as-promising-agents-for-alzheimer-s-disease-therapy
#18
Youssef Dgachi, Helène Martin, Alexandre Bonet, Mourad Chioua, Isabel Iriepa, Ignacio Moraleda, Fakher Chabchoub, José Marco-Contelles, Lhassane Ismaili
AIM: Due to the complex nature of Alzheimer's disease, there is a renewed search for multitarget directed drugs. RESULTS: This paper describes the synthesis and in vitro biological evaluation of six racemic 13-aryl-2,3,4,13-tetrahydro-1H,12H-benzo[6,7]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-7,12,14-triones (1a-6a), and six racemic 15-aryl-8,9,10,11,12,15-hexahydro-14H-benzo[6',7']chromeno[2',3:4,5] pyr-imido [1,2-a]azepine-5,14,16-triones (1b-6b), showing antioxidant and cholinesterase inhibitory capacity...
May 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28503814/diabetes-mellitus-and-risk-of-early-onset-alzheimer-s-disease-a-population-based-case-control-study
#19
K Kadohara, I Sato, K Kawakami
BACKGROUND AND PURPOSE: Previous studies have reported that diabetes is a risk factor for both all-cause and vascular dementia; however, diabetes as a risk factor for Alzheimer's disease (AD) remains controversial. Therefore, the aim was to elucidate the association between diabetes and early-onset AD. METHODS: A case-control study was conducted using a population-based database that included medical and pharmacy claims and insurance eligibility data, from beneficiaries of corporate employees and their dependent family members...
May 15, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28502042/tale-of-the-good-and-the-bad-cdk5-remodeling-of-the-actin-cytoskeleton-in-the-brain
#20
REVIEW
Kavita Shah, Sandra Rossie
Cdk5 kinase, a cyclin-dependent kinase family member, is a key regulator of cytoskeletal remodeling in the brain. Cdk5 is essential for brain development during embryogenesis. After birth, it is essential for numerous neuronal processes such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity is deregulated in various brain disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemic stroke, resulting in profound remodeling of the neuronal cytoskeleton, loss of synapses, and ultimately neurodegeneration...
May 13, 2017: Molecular Neurobiology
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