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Neurobiology of Aging

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https://www.readbyqxmd.com/read/28222900/genetic-analysis-of-the-sod1-and-c9orf72-genes-in-hungarian-patients-with-amyotrophic-lateral-sclerosis
#1
Kornélia Tripolszki, Bernadett Csányi, Dóra Nagy, Antonia Ratti, Cinzia Tiloca, Vincenzo Silani, Éva Kereszty, Nóra Török, László Vécsei, József I Engelhardt, Péter Klivényi, Nikoletta Nagy, Márta Széll
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons. To date, more than 20 genes have been implicated in ALS, and of these, the 2 most frequently mutated are the superoxide dismutase 1 (SOD1) gene and the chromosome 9 open reading frame 72 (C9ORF72) gene. In this study, we aimed to investigate the contribution of these 2 Mendelian genes to the development of the disease in Hungarian ALS patients (n = 66). Direct sequencing of the SOD1 gene revealed a novel (p...
January 29, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28202203/female-specific-effect-of-the-bdnf-gene-on-alzheimer-s-disease
#2
Guo-Dong Li, Rui Bi, Deng-Feng Zhang, Min Xu, Rongcan Luo, Dong Wang, Yiru Fang, Tao Li, Chen Zhang, Yong-Gang Yao
Alzheimer's disease (AD) is the most common neurodegenerative disease influenced by genetic and environmental factors. Brain-derived neurotrophic factor (BDNF) plays an important role in the progression of AD, but the genetic association between BDNF and AD remains controversial. In this study, we aimed to explore the potential association between genetic variants in BDNF and AD in Han Chinese and to investigate whether the association is affected by gender. A 3-stage study was conducted to evaluate the genetic association between BDNF and AD...
January 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28214109/a-novel-mutation-in-trem2-gene-causing-nasu-hakola-disease-and-review-of-the-literature
#3
Efthimios Dardiotis, Vasileios Siokas, Eva Pantazi, Maria Dardioti, Dimitrios Rikos, Georgia Xiromerisiou, Aikaterini Markou, Dimitra Papadimitriou, Matthaios Speletas, Georgios M Hadjigeorgiou
Nasu-hakola disease (NHD) is a rare disease characterized by bone cysts and fractures, frontal lobe syndrome, and progressive presenile dementia. NHD may be the prototype of primary microglial disorders of the CNS or, as they have been coined, "microgliopathies". Mutations in TREM2 and TYROBP genes are known to cause NHD. Interestingly, recent evidence-associated rare genetic variants of TREM2 gene with increased risk of Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Parkinson's disease...
January 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28208063/white-matter-lesions-and-the-cholinergic-deficit-in-aging-and-mild-cognitive-impairment
#4
Nils Richter, Anne Michel, Oezguer A Onur, Lutz Kracht, Markus Dietlein, Marc Tittgemeyer, Bernd Neumaier, Gereon R Fink, Juraj Kukolja
In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [(11)C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants...
January 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28189924/association-between-csf-biomarkers-hippocampal-volume-and-cognitive-function-in-patients-with-amnestic-mild-cognitive-impairment-mci
#5
Pradeep J Nathan, Yen Ying Lim, Rosemary Abbott, Samantha Galluzzi, Moira Marizzoni, Claudio Babiloni, Diego Albani, David Bartres-Faz, Mira Didic, Lucia Farotti, Lucilla Parnetti, Nicola Salvadori, Bernhard W Müller, Gianluigi Forloni, Nicola Girtler, Tilman Hensch, Jorge Jovicich, Annebet Leeuwis, Camillo Marra, José Luis Molinuevo, Flavio Nobili, Jeremie Pariente, Pierre Payoux, Jean-Philippe Ranjeva, Elena Rolandi, Paolo Maria Rossini, Peter Schönknecht, Andrea Soricelli, Magda Tsolaki, Pieter Jelle Visser, Jens Wiltfang, Jill C Richardson, Régis Bordet, Olivier Blin, Giovanni B Frisoni
Few studies have examined the relationship between CSF and structural biomarkers, and cognitive function in MCI. We examined the relationship between cognitive function, hippocampal volume and cerebrospinal fluid (CSF) Aβ42 and tau in 145 patients with MCI. Patients were assessed on cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Geriatric Depression Scale and the Functional Activities Questionnaire. Hippocampal volume was measured using magnetic resonance imaging (MRI), and CSF markers of Aβ42, tau and p-tau181 were also measured...
January 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28192686/the-down-syndrome-brain-in-the-presence-and-absence-of-fibrillar-%C3%AE-amyloidosis
#6
Tiina Annus, Liam R Wilson, Julio Acosta-Cabronero, Arturo Cardenas-Blanco, Young T Hong, Tim D Fryer, Jonathan P Coles, David K Menon, Shahid H Zaman, Anthony J Holland, Peter J Nestor
People with Down syndrome (DS) have a neurodevelopmentally distinct brain and invariably developed amyloid neuropathology by age 50. This cross-sectional study aimed to provide a detailed account of DS brain morphology and the changes occuring with amyloid neuropathology. Forty-six adults with DS underwent structural and amyloid imaging-the latter using Pittsburgh compound B (PIB) to stratify the cohort into PIB-positive (n = 19) and PIB-negative (n = 27). Age-matched controls (n = 30) underwent structural imaging...
January 17, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28189343/early-upregulation-of-18-kda-translocator-protein-in-response-to-acute-neurodegenerative-damage-in-trem2-deficient-mice
#7
Sara Belloli, Maria Pannese, Cecilia Buonsanti, Chiara Maiorino, Giuseppe Di Grigoli, Assunta Carpinelli, Cristina Monterisi, Rosa Maria Moresco, Paola Panina-Bordignon
Mutations in the TREM2 gene confer risk for Alzheimer's disease and susceptibility for Parkinson's disease (PD). We evaluated the effect of TREM2 deletion in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, measuring neurodegeneration and microglia activation using a combined in vivo imaging and postmortem molecular approach. In wild-type mice, MPTP administration induced a progressive decrease of [(11)C]FECIT uptake, culminating at day 7. Neuronal loss was accompanied by an increase of TREM2, IL-1β, and translocator protein (TSPO) transcript levels, [(11)C]PK11195 binding and GFAP staining (from day 2), and an early and transient increase of TNF-α, Galectin-3, and Iba-1 (from day 1)...
January 17, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28185661/age-related-deficits-in-auditory-temporal-processing-unique-contributions-of-neural-dyssynchrony-and-slowed-neuronal-processing
#8
Kelly C Harris, Judy R Dubno
This study was guided by the hypothesis that the aging central nervous system progressively loses its ability to process rapid acoustic changes that are important for speech recognition. Specifically, we hypothesized that age-related deficits in neural synchrony and neuronal oscillatory activity occur independently in older adults and disrupt auditory temporal processing. Neural synchrony is largely dependent on phase locking within the central auditory pathway, beginning at the auditory nerve. In contrast, the resonance characteristics of oscillatory activity are dependent on the integrity and structure of long range cortical connections...
January 16, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28212893/traffic-related-air-pollution-impact-on-mouse-brain-accelerates-myelin-and-neuritic-aging-changes-with-specificity-for-ca1-neurons
#9
Nicholas C Woodward, Payam Pakbin, Arian Saffari, Farimah Shirmohammadi, Amin Haghani, Constantinos Sioutas, Mafalda Cacciottolo, Todd E Morgan, Caleb E Finch
Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter <2.5-μm diameter (PM2.5). Rodents exposed to TRAP have shown microglial activation and neuronal atrophy. We further investigated age differences of TRAP exposure, with focus on hippocampus for neuritic atrophy, white matter degeneration, and microglial activation. Young- and middle-aged mice (3 and 18 months female C57BL/6J) were exposed to nanoscale-PM (nPM, <0...
January 13, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28185662/alphab-crystallin-expression-correlates-with-aging-deficits-in-the-peripheral-nervous-system
#10
Erin-Mai F Lim, Alim Musa, Ariana Frederick, Shalina S Ousman
In an effort to identify factors that contribute to age-related deficits in the undamaged and injured peripheral nervous system (PNS), we noted that Brady and colleagues found that mice null for a small heat shock protein called alphaB-crystallin (αBC) developed abnormalities early in life that are reminiscent of aging pathologies. Because of our observation that αBC protein levels markedly reduce as wild-type mice age, we investigated whether the crystallin plays a role in modulating age-related deficits in the uninjured and damaged PNS...
January 12, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28157554/running-induced-memory-enhancement-correlates-with-the-preservation-of-thin-spines-in-the-hippocampal-area-ca1-of-old-c57bl-6-mice
#11
Benke Xu, Anbang Sun, Yun He, Feng Qian, Lian Liu, Yuncai Chen, Huanmin Luo
The effects of prolonged physical training on memory performance and underlying synaptic mechanisms were investigated in old C57BL/6 mice. Training via voluntary running wheels was initiated at 16 months of age and continued for 5 months (1 hour per day and 5 days per week), followed by learning and memory test and spine/synapse analysis. Trained old mice were compared with their age-matched sedentary controls and aged adult controls. This training improved hippocampal-dependent spatial learning and memory function in old mice, and enhanced cognition was accompanied by increased density of spines on CA1 pyramidal cells in the hippocampus...
January 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28153381/ric3-variants-are-not-associated-with-parkinson-s-disease-in-french-canadians-and-french
#12
Jay P Ross, Nicolas Dupré, Yves Dauvilliers, Stephanie Strong, Alexandre Dionne-Laporte, Patrick A Dion, Guy A Rouleau, Ziv Gan-Or
Variants in the RIC3 gene have recently been suggested as a novel cause of Parkinson's disease (PD). Herein, the entire RIC3 gene was sequenced in a French-Canadian and French sample series of 535 PD patients and 527 unaffected controls. The effect of single variants and the combined effect of variants were calculated. Sequence Kernel association tests (SKAT, SKAT-O) were done on the entire gene level, and on the different domains and exons of RIC3. A total of 28 common and rare variants were identified in patients and controls...
January 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28160950/comprehensive-targeted-next-generation-sequencing-in-japanese-familial-amyotrophic-lateral-sclerosis
#13
Ayumi Nishiyama, Tetsuya Niihori, Hitoshi Warita, Rumiko Izumi, Tetsuya Akiyama, Masaaki Kato, Naoki Suzuki, Yoko Aoki, Masashi Aoki
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by loss of motor neurons. We have recently identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan. To reveal possible genetic causes for the remaining 51 patients with familial ALS (45 pedigrees), we performed targeted next-generation sequencing of 35 known ALS/motor neuron diseases-related genes. Known variants in ANG, OPTN, SETX, and TARDBP were identified in 6 patients...
January 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28129566/aging-retinal-function-is-improved-by-near-infrared-light-670%C3%A2-nm-that-is-associated-with-corrected-mitochondrial-decline
#14
Chrishne Sivapathasuntharam, Sobha Sivaprasad, Christopher Hogg, Glen Jeffery
Aging is associated with cellular decline and reduced function, partly mediated by mitochondrial compromise. However, aged mitochondrial function is corrected with near infrared light (670 nm) that improves their membrane potentials and adenosine triphosphate production and also reduces age-related inflammation. We ask if 670 nm light can also improve declining retinal function. Electroretinograms were measured in 2-, 7-, and 12-month old C57BL/6 mice. Significant age-related declines were measured in the photoreceptor generated a-wave and the postreceptoral b-wave...
January 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28153380/grn-deletion-in-familial-frontotemporal-dementia-showing-association-with-clinical-variability-in-3-familial-cases
#15
Graziella Milan, Sabrina Napoletano, Sabina Pappatà, Maria Teresa Gentile, Luca Colucci-D'Amato, Gennaro Della Rocca, Anna Maciag, Carmen Palermo Rossetti, Laura Fucci, Annibale Puca, Dario Grossi, Alfredo Postiglione, Emilia Vitale
Progranulin (GRN) gene mutations have been genetically associated with frontotemporal dementia (FTD) and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of 3 pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritance patterns. We present evidence that all the available patients in these 3 familial cases are carrying the rare GRN gene exon 6 deletion g10325_10331delCTGCTGT (relative to nt 1 inNG_007886...
January 9, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28131462/gene-based-association-study-of-genes-linked-to-hippocampal-sclerosis-of-aging-neuropathology-grn-tmem106b-abcc9-and-kcnmb2
#16
Yuriko Katsumata, Peter T Nelson, Sally R Ellingson, David W Fardo
Hippocampal sclerosis of aging (HS-Aging) is a common neurodegenerative condition associated with dementia. To learn more about genetic risk of HS-Aging pathology, we tested gene-based associations of the GRN, TMEM106B, ABCC9, and KCNMB2 genes, which were reported to be associated with HS-Aging pathology in previous studies. Genetic data were obtained from the Alzheimer's Disease Genetics Consortium, linked to autopsy-derived neuropathological outcomes from the National Alzheimer's Coordinating Center. Of the 3251 subjects included in the study, 271 (8...
January 9, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28113088/gamma-oscillatory-activity-is-impaired-in-episodic-memory-encoding-with-age
#17
Olivier Després, Ségolène Lithfous, Delphine Tromp, Thierry Pebayle, André Dufour
The present study proposes to investigate age-related episodic memory impairment in encoding. We collected ERPs in young and old participants performing a word-encoding task. For subsequently remembered words, young adults had greater activity at the left and anterior electrode sites, whereas old adults had greater posterior activity. Performance correlated positively with central sites in young adults but with left parietal hemisphere activity in old adults. Plus, a large left frontoparietal network increased its activity during the successful encoding for the Beta (13-30 Hz) and Gamma (30-100 Hz) bands in young adults...
January 9, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28208064/mitochondrial-genes-are-altered-in-blood-early-in-alzheimer-s-disease
#18
Katie Lunnon, Aoife Keohane, Ruth Pidsley, Stephen Newhouse, Joanna Riddoch-Contreras, Elisabeth B Thubron, Matthew Devall, Hikka Soininen, Iwona Kłoszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Leonard Schalkwyk, Richard Dobson, Afshan N Malik, John Powell, Simon Lovestone, Angela Hodges
Although mitochondrial dysfunction is a consistent feature of Alzheimer's disease in the brain and blood, the molecular mechanisms behind these phenomena are unknown. Here we have replicated our previous findings demonstrating reduced expression of nuclear-encoded oxidative phosphorylation (OXPHOS) subunits and subunits required for the translation of mitochondrial-encoded OXPHOS genes in blood from people with Alzheimer's disease and mild cognitive impairment. Interestingly this was accompanied by increased expression of some mitochondrial-encoded OXPHOS genes, namely those residing closest to the transcription start site of the polycistronic heavy chain mitochondrial transcript (MT-ND1, MT-ND2, MT-ATP6, MT-CO1, MT-CO2, MT-C03) and MT-ND6 transcribed from the light chain...
January 7, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28131463/very-early-onset-sporadic-alzheimer-s-disease-with-a-de-novo-mutation-in-the-psen1-gene
#19
Fan Lou, Xiaoguang Luo, Ming Li, Yan Ren, Zhiyi He
We report a 22-year onset age man diagnosed with rapidly progressing early-onset Alzheimer's disease with predominant extrapyramidal symptoms as the initial presenting symptoms and V391G mutation in presenilin 1 gene (PSEN1) was founded. The unaffected parents of the proband are not carriers of the mutation but have histories of extrapyramidal diseases, suggesting de novo origin of V391G mutation. The Val391Gly variation widens the number of PSEN1 mutations responsible for early-onset Alzheimer's disease with extrapyramidal phenotype and would help to establish a functional map of presenilin 1 protein architecture...
January 6, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28131016/rod-shaped-microglia-morphology-is-associated-with-aging-in-2-human-autopsy-series
#20
Adam D Bachstetter, Eseosa T Ighodaro, Yasmin Hassoun, Danah Aldeiri, Janna H Neltner, Ela Patel, Erin L Abner, Peter T Nelson
A subtype of microglia is defined by the morphological appearance of the cells as rod shaped. Little is known about this intriguing cell type, as there are only a few case reports describing rod-shaped microglia in the neuropathological literature. Rod-shaped microglia were shown recently to account for a substantial proportion of the microglia cells in the hippocampus of both demented and cognitively intact aged individuals. We hypothesized that aging could be a defining feature in the occurrence of rod-shaped microglia...
January 5, 2017: Neurobiology of Aging
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