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Familial Alzheimer's disease

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https://www.readbyqxmd.com/read/28429562/predictors-of-the-health-related-quality-of-life-of-chinese-people-with-major-neurocognitive-disorders-and-their-caregivers-the-roles-of-self-esteem-and-caregiver-s-burden
#1
Daniel Kim-Wan Young, Petrus Yat-Nam Ng, Timothy Kwok
AIM: The present research study aimed to identify and compare the clinical and non-clinical factors that predict the self-reported and proxy-reported health-related quality of life (HRQoL) of people with major neurocognitive disorder (PwND) who are living at home in a Chinese society. METHODS: A total of 57 Chinese PwND-family caregiver dyads that were using the services of local senior centers were recruited through a cross-sectional survey with convenience sampling...
April 20, 2017: Geriatrics & Gerontology International
https://www.readbyqxmd.com/read/28424614/relationship-between-cognitive-and-sleep-wake-variables-in-asymptomatic-offspring-of-patients-with-late-onset-alzheimer-s-disease
#2
Carolina Abulafia, Bárbara Duarte-Abritta, Mirta F Villarreal, María S Ladrón-de-Guevara, Celeste García, Geraldine Sequeyra, Gustavo Sevlever, Leticia Fiorentini, Karl-Jürgen Bär, Deborah R Gustafson, Daniel E Vigo, Salvador M Guinjoan
Early neuropathological changes characteristic of late-onset Alzheimer's disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily temperature...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28422708/a-brief-essay-on-non-pharmacological-treatment-of-alzheimer-s-disease
#3
Alberto Raggi, Domenica Tasca, Raffaele Ferri
Current pharmacological therapies for Alzheimer's disease (AD) do not modify its course and are not always beneficial. Therefore, the optimization of quality of life represents the best possible outcome achievable in all stages of the disease. Cognitive and behavioural rehabilitation represents the main therapeutic approach for this purpose, also in order to mitigate indirectly the burden of distress of family caregivers. The aim of this mini-review is to go through this theme by discussing cognitive activation, virtual reality and neuromodulation techniques...
April 19, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28420962/dysregulation-of-rna-binding-protein-aggregation-in-neurodegenerative-disorders
#4
REVIEW
Brandon Maziuk, Heather I Ballance, Benjamin Wolozin
The unique biology of RNA binding proteins is altering our view of the genesis of protein misfolding diseases. These proteins use aggregation of low complexity domains (LCDs) as a means to regulate the localization and utilization of RNA by forming RNA granules, such as stress granules, transport granules and P-bodies. The reliance on reversible aggregation as a mechanism for biological regulation renders this family of proteins highly vulnerable to promoting diseases of protein misfolding. Mutations in RNA binding proteins are associated with many neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28418403/assessing-the-presence-of-shared-genetic-architecture-between-alzheimer-s-disease-and-major-depressive-disorder-using-genome-wide-association-data
#5
J Gibson, T C Russ, M J Adams, T-K Clarke, D M Howard, L S Hall, A M Fernandez-Pujals, E M Wigmore, C Hayward, G Davies, A D Murray, B H Smith, D J Porteous, I J Deary, A M McIntosh
Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28417423/evaluation-of-the-expression-of-amyloid-precursor-protein-and-the-ratio-of-secreted-amyloid-beta-42-to-amyloid-beta-40-in-sh-sy5y-cells-stably-transfected-with-wild-type-single-mutant-and-double-mutant-forms-of-the-app-gene-for-the-study-of-alzheimer-s-disease
#6
Aslina Pahrudin Arrozi, Siti Nur Syazwani Shukri, Wan Zurinah Wan Ngah, Yasmin Anum Mohd Yusof, Mohd Hanafi Ahmad Damanhuri, Suzana Makpol
Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models in neurodegenerative research, and their use has advanced the understanding of the pathology of neurodegeneration over the past few decades. In Alzheimer's disease (AD), several pathogenic mutations have been described, all of which cause elevated levels of pathological hallmarks such as amyloid-beta (Aβ). Although the genetics of Alzheimer's disease is well known, familial AD only accounts for a small number of cases in the population, with the rest being sporadic AD, which contains no known mutations...
April 17, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28416393/tdp-43-expression-influences-amyloid%C3%AE-plaque-deposition-and-tau-aggregation
#7
Stephani A Davis, Kok Ann Gan, James A Dowell, Nigel J Cairns, Michael A Gitcho
Although the main focus in Alzheimer's disease (AD) has been an investigation of mechanisms causing Aβ plaque deposition and tau tangle formation, recent studies have shown that phosphorylated TDP-43 pathology is present in up to 50% of sporadic cases. Furthermore, elevated phosphorylated TDP-43 has been associated with more severe AD pathology. Therefore, we hypothesized that TDP-43 may regulate amyloid-beta precursor protein (APP) trafficking and tau phosphorylation/aggregation. In order to examine the role of TDP-43 in AD, we developed a transgenic mouse that overexpresses hippocampal and cortical neuronal TDP-43 in a mouse expressing familial mutations (K595N and M596L) in APP and presenilin 1 (PSEN1ΔE9)...
April 14, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28413778/family-history-and-apoe4-risk-for-alzheimer-s-disease-impact-the-neural-correlates-of-episodic-memory-by-early-midlife
#8
M N Rajah, L M K Wallace, E Ankudowich, E H Yu, A Swierkot, R Patel, M M Chakravarty, D Naumova, J Pruessner, R Joober, S Gauthier, S Pasvanis
Episodic memory impairment is a consistent, pronounced deficit in pre-clinical stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for AD exhibit altered brain function several decades prior to the onset of AD-related symptoms. In the current event-related fMRI study of spatial context memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a family history of late onset AD (MA+ FH), or a combined + FH and apolipoprotein E ε4 allele risk factors for AD (MA+ FH + APOE4), will exhibit differences in encoding and retrieval-related brain activity, compared to - FH - APOE4 MA controls...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28412672/relationship-between-alzheimer-s-disease-and-mitochondria-coenzyme-ii-gene
#9
Chen Liangmei, Chen Ying, Liu Feihu, He Changjiang, Zhang Luying, He Dingxiong, Ao Lei
We aimed to investigate the relevance between Alzheimer's disease (AD) and gene mutations of mitochondrial cytochrome oxidase subunit III (COX3) and coenzyme II (ND2), and to provide genetic markers for the diagnosis of Alzheimer's disease (AD) and further provide some feasible basis for preventive treatment. Polymerase chain reaction-restriction fragment length polymorphism technique was used, and genotypes and gene frequencies were detected in 60 patients with Alzheimer's disease (AD), who meet the ICD-10 diagnostic criteria (AD group), 10 AD families and 60 normal old people (control group)...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28410120/snp_tata_comparator-genomewide-landmarks-for-preventive-personalized-medicine
#10
Mikhail Ponomarenko, Dmitry Rasskazov, Irina Chadaeva, Ekaterina Sharypova, Petr Ponomarenko, Olga Arkova, Elena Kashina, Nikita Ivanisenko, Dmitry Zhechev, Ludmila Savinkova, Nikolay Kolchanov
Year after year, conditions, quality, and duration of human lives have been improving due to the progress of science, technology, education, and medicine, which however has a downside. Owing to improvement in children's nutrition, developmental acceleration occurs that imbalances a child's system. Because of virtual worlds of the Internet, social experience of teenagers expands and clashes with puberty of adolescents. Due to the comfort of cities, urbanization emerges and causes stress to adults because of artificial light, noise, pollution, violations of personal space, and family disruption...
June 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28409746/the-role-of-adam10-in-alzheimer-s-disease
#11
Xiang-Zhen Yuan, Sen Sun, Chen-Chen Tan, Jin-Tai Yu, Lan Tan
As a member of the A Disintegrin And Metalloproteinase (ADAM) family, ADAM10 has been identified as the constitutive α-secretase in the process of amyloid-β protein precursor (AβPP) cleavage and plays a critical role in reducing the generation of the amyloid-β (Aβ) peptides. Recent studies have demonstrated its beneficial role in alleviating the pathologic impairment in Alzheimer's disease (AD) both in vitro and in vivo. However, the role of ADAM10 in AD and the underlying molecular mechanisms are still not well established...
April 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28408880/a-bayesian-model-for-the-prediction-and-early-diagnosis-of-alzheimer-s-disease
#12
Athanasios Alexiou, Vasileios D Mantzavinos, Nigel H Greig, Mohammad A Kamal
Alzheimer's disease treatment is still an open problem. The diversity of symptoms, the alterations in common pathophysiology, the existence of asymptomatic cases, the different types of sporadic and familial Alzheimer's and their relevance with other types of dementia and comorbidities, have already created a myth-fear against the leading disease of the twenty first century. Many failed latest clinical trials and novel medications have revealed the early diagnosis as the most critical treatment solution, even though scientists tested the amyloid hypothesis and few related drugs...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28402542/positive-affect-predicts-cerebral-glucose-metabolism-in-late-middle-aged-adults
#13
Christopher Nicholas, Siobhan M Hoscheidt, Lindsay R Clark, Annie M Racine, Sara E Berman, Rebecca L Koscik, N Maritza Dowling, Sanjay Asthana, Bradley T Christian, Mark A Sager, Sterling C Johnson
Positive affect is associated with a number of health benefits; however, few studies have examined the relationship between positive affect and cerebral glucose metabolism, a key energy source for neuronal function and a possible index of brain health. We sought to determine if positive affect was associated with cerebral glucose metabolism in late middle-aged adults (n =134). Participants completed the positive affect subscale of the Center for Epidemiological Studies of Depression Scale (CES-D) at two time points over a two-year period and underwent FDG-PET scanning...
April 11, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/28401371/glutamate-toxicity-to-differentiated-neuroblastoma-n2a-cells-is-prevented-by-the-sesquiterpene-lactone-achillolide-a-and-the-flavonoid-3-5-4-trihydroxy-6-7-3-trimethoxyflavone-from-achillea-fragrantissima
#14
Anat Elmann, Alona Telerman, Rivka Ofir, Yoel Kashman
Glutamate toxicity is a major contributor to the pathophysiology of numerous neurodegenerative diseases including amyotrophic lateral sclerosis and Alzheimer's disease. Therefore, protecting neuronal cells against glutamate-induced cytotoxicity might be an effective approach for the treatment of these diseases. We have previously purified from the medicinal plant Achillea fragrantissima two bioactive compounds which were not studied before: the sesquiterpene lactone achillolide A and the flavonoid 3,5,4'-trihydroxy-6,7,3'-trimethoxyflavone (TTF)...
April 11, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28400126/targeted-sequencing-of-abca7-identifies-splicing-stop-gain-and-intronic-risk-variants-for-alzheimer-disease
#15
B W Kunkle, R M Carney, M A Kohli, A C Naj, K L Hamilton-Nelson, P L Whitehead, L Wang, R Lang, M L Cuccaro, J M Vance, G S Byrd, G W Beecham, J R Gilbert, E R Martin, J L Haines, M A Pericak-Vance
Several variants in the gene ABCA7 have been identified as potential causal variants for late-onset Alzheimer's disease (LOAD). In order to replicate these findings, and search for novel causal variants, we performed targeted sequencing of this gene in cohorts of non-Hispanic White (NHW) and African-American (AA) LOAD cases and controls. We sequenced the gene ABCA7 in 291 NHW LOAD cases and 103 controls. Variants were prioritized for rare, damaging variants and previously reported variants associated with LOAD, and were follow-up genotyped in 4,076 NHW and 1,157 AA cases and controls...
April 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28400058/the-snk-and-spar-signaling-pathway-changes-in-hippocampal-neurons-treated-with-amyloid-beta-peptide-in-vitro
#16
Hua Sui, Libin Zhan, Xinping Niu, Lina Liang, Xin Li
Amyloid-β peptide (Aβ) is believed to be a primary cause of Alzheimer's disease. Many studies have demonstrated that Aβ causes morphological and functional alterations of dendritic spines, leading to synaptic dysfunction, but the effect of Aβ on damage to synaptic functions is not fully understood. Spine-associated Rap guanosine triphosphatase-activating protein (SPAR) is an important regulator of activity-dependent remodeling of synapses and is critically involved in both mature dendritic spine formation and the maintenance of spine maturity...
March 22, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28392767/early-onset-network-hyperexcitability-in-presymptomatic-alzheimer-s-disease-transgenic-mice-is-suppressed-by-passive-immunization-with-anti-human-app-a%C3%AE-antibody-and-by-mglur5-blockade
#17
Syed F Kazim, Shih-Chieh Chuang, Wangfa Zhao, Robert K S Wong, Riccardo Bianchi, Khalid Iqbal
Cortical and hippocampal network hyperexcitability appears to be an early event in Alzheimer's disease (AD) pathogenesis, and may contribute to memory impairment. It remains unclear if network hyperexcitability precedes memory impairment in mouse models of AD and what are the underlying cellular mechanisms. We thus evaluated seizure susceptibility and hippocampal network hyperexcitability at ~3 weeks of age [prior to amyloid beta (Aβ) plaque deposition, neurofibrillary pathology, and cognitive impairment] in a triple transgenic mouse model of familial AD (3xTg-AD mouse) that harbors mutated human Aβ precursor protein (APP), tau and presenilin 1 (PS1) genes...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28389559/the-kim-family-protein-tyrosine-phosphatases-use-distinct-reversible-oxidation-intermediates-intramolecular-or-intermolecular-disulfide-bond-formation
#18
Luciana E S F Machado, Tun-Li Shen, Rebecca Page, Wolfgang Peti
The kinase interaction motif (KIM) family of protein tyrosine phosphatases (PTPs) includes hematopoietic protein tyrosine phosphatase (HePTP), striatal-enriched protein tyrosine phosphatase (STEP), and protein tyrosine phosphatase receptor type R (PTPRR). KIM-PTPs bind and dephosphorylate mitogen activated protein kinases (MAPKs) and thereby critically modulate cell proliferation and differentiation. PTP activity can readily be diminished by reactive oxygen species (ROS), e.g. H2O2, that oxidize the catalytically indispensable active-site cysteine...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28389477/efad-transgenic-mice-as-a-human-apoe-relevant-preclinical-model-of-alzheimer-s-disease
#19
Leon M Tai, Deebika Balu, Evangelina Avila-Munoz, Laila Abdullah, Riya Thomas, Nicole Collins, Ana Carolina Valencia-Olvera, Mary Jo LaDu
Identified in 1993, APOE4 is the greatest genetic risk factor for sporadic Alzheimers disease (AD), increasing risk up to 12-fold compared to APOE3, with APOE2 decreasing AD risk. However, the functional effects of APOE4 on AD pathology remain unclear and, in some cases, controversial. In vivo progress to understand how the human (h)-APOE genotypes effect AD pathology has been limited by the lack of a tractable familial AD-transgenic (FAD-Tg) mouse model expressing h- rather than mouse (m)-APOE. The disparity between m- and h-apoE is relevant for virtually every AD-relevant pathway, including amyloid beta deposition and clearance, neuroinflammation, tau pathology, neural plasticity and cerebrovascular deficits...
April 7, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28387370/detection-of-prion-seeding-activity-in-the-olfactory-mucosa-of-patients-with-fatal-familial-insomnia
#20
Veronica Redaelli, Edoardo Bistaffa, Gianluigi Zanusso, Giulia Salzano, Luca Sacchetto, Martina Rossi, Chiara Maria Giulia De Luca, Michele Di Bari, Sara Maria Portaleone, Umberto Agrimi, Giuseppe Legname, Ignazio Roiter, Gianluigi Forloni, Fabrizio Tagliavini, Fabio Moda
Fatal Familial Insomnia (FFI) is a genetic prion disease caused by a point mutation in the prion protein gene (PRNP) characterized by prominent thalamic atrophy, diffuse astrogliosis and moderate deposition of PrP(Sc) in the brain. Here, for the first time, we demonstrate that the olfactory mucosa (OM) of patients with FFI contains trace amount of PrP(Sc) detectable by PMCA and RT-QuIC. Quantitative PMCA analysis estimated a PrP(Sc) concentration of about 1 × 10(-14) g/ml. In contrast, PrP(Sc) was not detected in OM samples from healthy controls and patients affected by other neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and frontotemporal dementia...
April 7, 2017: Scientific Reports
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