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Familial Alzheimer's disease

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https://www.readbyqxmd.com/read/28647363/cadps2-gene-expression-is-oppositely-regulated-by-lrrk2-and-alpha-synuclein
#1
Julia Obergasteiger, Christa Überbacher, Peter P Pramstaller, Andrew A Hicks, Corrado Corti, Mattia Volta
The Ca(2+)-dependent activator protein for secretion 2 (CADPS2) is a member of the CAPS/CADPS protein family that play crucial roles in synaptic vesicle dynamics. Genomic variability in the CADPS2 gene has been associated to autism spectrum disorders and Alzheimer's disease, both characterized by altered neurotransmission. Biological evidence also linked CADPS2 to Parkinson's disease (PD), as a disease-causing mutation in leucine-rich repeat kinase 2 (LRRK2) was reported to increase CADPS2 gene and protein expression...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28646794/dexibuprofen-prevents-neurodegeneration-and-cognitive-decline-in-appswe-ps1de9-through-multiple-signaling-pathways
#2
Miren Ettcheto, Elena Sánchez-López, Laura Pons, Oriol Busquets, Jordi Olloquequi, Carlos Beas-Zarate, Merce Pallas, Maria Luisa García, Carme Auladell, Jaume Folch, Antoni Camins
The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28646119/rest-suppression-mediates-neural-conversion-of-adult-human-fibroblasts-via-microrna-dependent-and-independent-pathways
#3
Janelle Drouin-Ouellet, Shong Lau, Per Ludvik Brattås, Daniella Rylander Ottosson, Karolina Pircs, Daniela A Grassi, Lucy M Collins, Romina Vuono, Annika Andersson Sjöland, Gunilla Westergren-Thorsson, Caroline Graff, Lennart Minthon, Håkan Toresson, Roger A Barker, Johan Jakobsson, Malin Parmar
Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons (iNs), was achieved for the first time 6 years ago. This technology offers a promising shortcut for obtaining patient- and disease-specific neurons for disease modeling, drug screening, and other biomedical applications. However, fibroblasts from adult donors do not reprogram as easily as fetal donors, and no current reprogramming approach is sufficiently efficient to allow the use of this technology using patient-derived material for large-scale applications...
June 23, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28645294/3-5-4-trihydroxy-6-7-3-trimethoxyflavone-protects-against-beta-amyloid-induced-neurotoxicity-through-antioxidative-activity-and-interference-with-cell-signaling
#4
Alona Telerman, Rivka Ofir, Yoel Kashman, Anat Elmann
BACKGROUND: Alzheimer's disease is a neurodegenerative disease, characterized by progressive decline in memory and cognitive functions, that results from loss of neurons in the brain. Amyloid beta (Aβ) protein and oxidative stress are major contributors to Alzheimer's disease, therefore, protecting neuronal cells against Aβ-induced toxicity and oxidative stress might form an effective approach for treatment of this disease. 3,5,4'-trihydroxy-6,7,3'-trimethoxyflavone (TTF) is a flavonoid we have purified from the plant Achillea fragrantissima; and the present study examined, for the first time, the effects of this compound on Aβ-toxicity to neuronal cells...
June 23, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28641509/brain-information-sharing-during-visual-short-term-memory-binding-yields-a-memory-biomarker-for-familial-alzheimer-s-disease
#5
Mario A Parra, Ezequiel Mikulan, Natalia Trujillo, Sergio Della Sala, Francisco Lopera, Facundo Manes, John Starr, Agustin Ibanez
BACKGROUND: Alzheimer's disease (AD) as a disconnection syndrome disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions are shared pathophysiological mechanisms remains unknown. OBJECTIVE: To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. METHODS: Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the VSTM binding test (VSTMBT) while we recorded their EEG...
June 14, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28641164/protective-effects-of-flavonoids-against-alzheimer-s-disease-related-neural-dysfunctions
#6
REVIEW
Mahsa Bakhtiari, Yunes Panahi, Javad Ameli, Behrad Darvishi
Senile ages of human life is mostly associated with developmental of several neurological complicated conditions including decreased cognition and reasoning, increased memory loss and impaired language performance. Alzheimer's disease (AD) is the most prevalent neural disorder associated with dementia, consisting of about 70% of dementia reported cases. Failure of currently approved chemical anti-AD therapeutic agents has once again brought up the idea of administering naturally occurring compounds as effective alternative and/or complementary regimens in AD treatment...
June 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28638323/sortilin-fragments-deposit-at-senile-plaques-in-human-cerebrum
#7
Xia Hu, Zhao-Lan Hu, Zheng Li, Chun-Sheng Ruan, Wen-Ying Qiu, Aihua Pan, Chang-Qi Li, Yan Cai, Lu Shen, Yaping Chu, Bei-Sha Tang, Huaibin Cai, Xin-Fu Zhou, Chao Ma, Xiao-Xin Yan
Genetic variations in the vacuolar protein sorting 10 protein (Vps10p) family have been linked to Alzheimer's disease (AD). Here we demonstrate deposition of fragments from the Vps10p member sortilin at senile plaques (SPs) in aged and AD human cerebrum. Sortilin changes were characterized in postmortem brains with antibodies against the extracellular and intracellular C-terminal domains. The two antibodies exhibited identical labeling in normal human cerebrum, occurring in the somata and dendrites of cortical and hippocampal neurons...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28636676/mitochondrion-to-endoplasmic-reticulum-apposition-length-in-zebrafish-embryo-spinal-progenitors-is-unchanged-in-response-to-perturbations-associated-with-alzheimer-s-disease
#8
Morgan Newman, Lena Halter, Anne Lim, Michael Lardelli
Mutations in the human genes PRESENILIN1 (PSEN1), PRESENILIN2 (PSEN2) and AMYLOID BETA A4 PRECURSOR PROTEIN (APP) have been identified in familial Alzheimer's disease (AD). The length of mitochondrion-endoplasmic reticulum (M-ER) appositions is increased in Psen1-/-/Psen2-/- double knockout murine embryonic fibroblasts and in fibroblasts from AD-affected individuals. Development of an easily accessible, genetically manipulable, in vivo system for studying M-ER appositions would be valuable so we attempted to manipulate M-ER apposition length in zebrafish (Danio rerio) embryos...
2017: PloS One
https://www.readbyqxmd.com/read/28635419/multimodal-imaging-gd-nanoparticles-functionalized-with-pittsburgh-compound-b-or-a-nanobody-for-amyloid-plaques-targeting
#9
Jonathan Pansieri, Marie Plissonneau, Nathalie Stransky-Heilkron, Mireille Dumoulin, Laurence Heinrich-Balard, Pascaline Rivory, Jean-François Morfin, Eva Toth, Maria Joao Saraiva, Eric Allémann, Olivier Tillement, Vincent Forge, François Lux, Christel Marquette
AIM: Gadolinium-based nanoparticles were functionalized with either the Pittsburgh compound B or a nanobody (B10AP) in order to create multimodal tools for an early diagnosis of amyloidoses. MATERIALS & METHODS: The ability of the functionalized nanoparticles to target amyloid fibrils made of β-amyloid peptide, amylin or Val30Met-mutated transthyretin formed in vitro or from pathological tissues was investigated by a range of spectroscopic and biophysics techniques including fluorescence microscopy...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#10
Fang Fang, Wanlin Yang, Jazmin B Florio, Edward Rockenstein, Brian Spencer, Xavier M Orain, Stephanie X Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633376/keeping-things-in-balance-family-experiences-of-living-with-alzheimer-s-disease
#11
Nuria Esandi, Mike Nolan, Cristina Alfaro, Ana Canga-Armayor
Background and Objectives: Historically, research, practice, and policy on Alzheimer's family care has been largely focused on dyadic relationships and the experience of burden and stress, often failing to capture the complex caring dynamics as they unfold over time. This study sought to develop a more nuanced understanding of how people with Alzheimer's disease (AD) and their families are affected by the disease and how they respond to the challenges AD poses. Research Design and Methods: Using constructivist grounded theory, the study explored the experiences of living with AD for native Spanish families residing in Navarra...
June 15, 2017: Gerontologist
https://www.readbyqxmd.com/read/28626014/bace1-cleavage-site-selection-critical-for-amyloidogenesis-and-alzheimer-s-pathogenesis
#12
Shuting Zhang, Zhe Wang, Fang Cai, Mingming Zhang, Yili Wu, Jing Zhang, Weihong Song
Mutations in amyloid β precursor protein (APP) gene alter APP processing, either causing familial Alzheimer's Disease (AD) or protecting against dementia. Under normal conditions beta-site APP cleaving enzyme 1 (BACE1) cleaves APP at minor Asp(1) site to generate C99 for amyloid β protein (Aβ) production, and predominantly at major Glu(11) site to generate C89, resulting in truncated Aβ production. We discovered that A673V mutation, the only recessive AD-associated APP mutation, shifted the preferential β-cleavage site of BACE1 in APP from the Glu(11) site to the Asp(1) site both in male and female transgenic mice in vivo and in cell lines and primary neuronal culture derived from timed pregnant rats in vitro, resulting in a much higher C99 level and C99/C89 ratio...
June 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28625939/promoting-the-maintenance-of-satisfactory-communication-strategies-used-by-caregivers-and-medical-staff-with-people-suffering-from-alzheimer-s-disease
#13
Marie Vachon, Marie-Christine Veilleux, Joël Macoir
The goal of this literature review was to determine communication strategies that foster interactions between individuals with Alzheimer's disease (AD) and caregivers or medical staff. A search of PubMed and PsycINFO databases was conducted using combinations of the following terms: Alzheimer, family, caregiver, communication, language, treatment, intervention, therapy, communication strategies, functional communication and daily living activities. Studies were chosen based on the original language of the text, year of publication, peer-review status and specificity of the results regarding communication strategies in AD...
June 1, 2017: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
https://www.readbyqxmd.com/read/28623607/presenilin-1-targeted-morpholino-induces-cognitive-deficits-increased-brain-a%C3%AE-1-42-and-decreased-synaptic-marker-psd-95-in-zebrafish-larvae
#14
Laura Roesler Nery, Natalia Eltz Silva, Raphaela Fonseca, Monica Ryff Moreira Vianna
Presenilins are transmembrane proteases required for the proteolytic cleavage of Notch and also act as the catalytic core of the γ-secretase complex, which is responsible for the final cleavage of the amyloid precursor protein into Amyloid-β (Aβ) peptides of varying lengths. Presenilin-1 gene (psen1) mutations are the main cause of early-onset autosomal-dominant Familial Alzheimer Disease. Elucidating the roles of Presenilin-1 and other hallmark proteins involved in Alzheimer's disease is crucial for understanding the disease etiology and underlying molecular mechanisms...
June 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28615451/molecular-mechanisms-of-signaling-via-the-docosanoid-neuroprotectin-d1-for-cellular-homeostasis-and-neuroprotection
#15
Aram Asatryan, Nicolas G Bazan
Docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member that is enriched in the nervous system, generates bioactive docosanoids that can counteract disruptions of cellular homeostasis. Docosanoids include neuroprotectin D1 (NPD1), which is decreased in the CA1 hippocampal area of patients with early-stage Alzheimers disease (AD). We summarize here how NPD1 elicits neuroprotection by up-regulating c-REL, a nuclear factor (NF)-kappaB subtype that, in turn, enhances expression of BIRC3 (baculoviral IAP repeat-containing protein 3, or cIAP2) in retinal cells...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28612294/the-potential-role-of-bmaa-in-neurodegeneration
#16
REVIEW
Tracie Caller, Patricia Henegan, Elijah Stommel
Neurodegenerative diseases are a major public health issue throughout the world with devastating effects on patients and families. Sporadic forms of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are generally thought to develop as a consequence of genetic susceptibility and environmental influences. A number of environmental triggers have been identified in association with amyotrophic lateral sclerosis and Parkinson's disease. We discuss the role of β-methylamino-L-alanine in the development of neurodegeneration and the potential importance of this neurotoxin as a risk for neurodegeneration...
June 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28612048/obesity-accelerates-alzheimer-related-pathology-in-apoe4-but-not-apoe3-mice
#17
V Alexandra Moser, Christian J Pike
Alzheimer's disease (AD) risk is modified by both genetic and environmental risk factors, which are believed to interact to cooperatively modify pathogenesis. Although numerous genetic and environmental risk factors for AD have been identified, relatively little is known about potential gene-environment interactions in regulating disease risk. The strongest genetic risk factor for late-onset AD is the ε4 allele of apolipoprotein E (APOE4). An important modifiable risk factor for AD is obesity, which has been shown to increase AD risk in humans and accelerate development of AD-related pathology in rodent models...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28605999/the-influence-of-psychosocial-and-cognitive-factors-on-perceived-threat-of-alzheimer-s-disease
#18
Jenny E Ostergren, Steven G Heeringa, Carlos F Mendes de Leon, Cathleen M Connell, J Scott Roberts
This study explored psychosocial and cognitive predictors of perceived threat of Alzheimer's disease (AD). Respondents were 1641 adults (mean age: 64.4; 54% female; 82% white) who completed a module in the Health and Retirement Study, a nationally representative survey of adults aged ≥50. Findings show that perceived threat was significantly higher for those aged 50 to 64 ( P < .001) and 65 to 74 ( P < .05) than for those ≥75. Respondents with a family history of AD had significantly greater perceived threat ( P < ...
January 1, 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28597200/the-lesion-analysis-of-cholinergic-neurons-in-5xfad-mouse-model-in-the-three-dimensional-level-of-whole-brain
#19
Huanhuan Yan, Pei Pang, Wenqi Chen, Houze Zhu, K A Henok, Hao Li, Zuoze Wu, Xiao Ke, Jianhua Wu, Tongmei Zhang, Kai Pan, Lei Pei, Yunyun Han, Youming Lu
Cholinergic system is very important for many higher brain functions, including learning and memory. Cholinergic neurons, especially those in the basal forebrain, are specifically susceptible in some neurodegenerative diseases, such as in Alzheimer's disease (AD). Here, we studied the cholinergic system lesion effects of five familial AD mutations in 5XFAD mice, a transgenic mouse model of AD. Although the cholinergic system has been studied in this mouse model, the cholinergic deficits in AD mice have never been systematically mapped in a whole-brain three-dimensional (3D) reconstruction...
June 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28596733/melatonin-supplementation-a-strategy-to-prevent-neurological-diseases-through-maintaining-integrity-of-blood-brain-barrier-in-old-people
#20
Wen-Cao Liu, Xiaona Wang, Xinyu Zhang, Xi Chen, Xinchun Jin
Blood brain barrier (BBB) plays a crucial role in maintaining homeostasis of microenvironment that is essential to neural function of the central nervous system (CNS). When facing various extrinsic or intrinsic stimuli, BBB is damaged which is an early event in pathogenesis of a variety of neurological diseases in old patients including acute and chronic cerebral ischemia, Alzheimer's disease and etc. Treatments that could maintain the integrity of BBB may prevent neurological diseases following various stimuli...
2017: Frontiers in Aging Neuroscience
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