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Neurobiology of Aging

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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
#1
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
#2
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/28528774/local-to-remote-cortical-connectivity-in-amnestic-mild-cognitive-impairment
#3
Yi-Wen Zhang, Zhi-Lian Zhao, Zhigang Qi, Yang Hu, Yin-Shan Wang, Can Sheng, Yu Sun, Xiaoni Wang, Li-Li Jiang, Chao-Gan Yan, Kuncheng Li, Hui-Jie Li, Xi-Nian Zuo
Alterations in both local and remote connectivity were reported in amnestic mild cognitive impairment (aMCI) patients but rarely in the same group of patients. In the present study, we employed a novel resting-state functional magnetic resonance imaging (rfMRI) connectome index, regional functional homogeneity on the 2-dimensional cortical surface, to detect full-cortex vertex-wise changes of the local rfMRI connectivity in 32 aMCI patients compared with 40 healthy controls. We further used the seed-based functional connectivity to explore the remote rfMRI connectivity in aMCI...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28528773/apoe-moderates-compensatory-recruitment-of-neuronal-resources-during-working-memory-processing-in-healthy-older-adults
#4
Elisa Scheller, Jessica Peter, Lena V Schumacher, Jacob Lahr, Irina Mader, Christoph P Kaller, Stefan Klöppel
The APOE ε4 allele increases the risk for sporadic Alzheimer's disease and modifies brain activation patterns of numerous cognitive domains. We assessed cognitively intact older adults with a letter n-back task to determine if previously observed increases in ε4 carriers' working-memory-related brain activation are compensatory such that they serve to maintain working memory function. Using multiple regression models, we identified interactions of APOE variant and age in bilateral hippocampus independently from task performance: ε4 carriers only showed a decrease in activation with increasing age, suggesting high sensitivity of fMRI data for detecting changes in Alzheimer's disease-relevant brain areas before cognitive decline...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28528772/early-interleukin-6-enhances-hepatic-ketogenesis-in-appswe-psen1de9-mice-via-3-hydroxy-3-methylglutary-coa-synthase-2-signaling-activation-by-p38-nuclear-factor-%C3%AE%C2%BAb-p65
#5
Le Shi, Daina Zhao, Chen Hou, Yunhua Peng, Jing Liu, Shuangxi Zhang, Jiankang Liu, Jiangang Long
Alzheimer's disease (AD) is considered a multifactorial disease that affects the central nervous system and periphery. A decline in brain glucose metabolism is an early feature of AD and is accompanied by a phenotypic shift from aerobic glycolysis to ketogenesis. The liver is responsible for the generation of the ketone body. However, the mechanism that underlies hepatic ketogenesis in AD remains unclear. Here, we investigated hepatic ketogenesis during the early stage of AD pathogenesis in amyloid precursor protein (APPSWE) and presenilin (PSEN1dE9) (APP/PS1) mice...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28527525/age-related-white-matter-integrity-differences-in-oldest-old-without-dementia
#6
Ilana J Bennett, Dana E Greenia, Pauline Maillard, S Ahmad Sajjadi, Charles DeCarli, Maria M Corrada, Claudia H Kawas
Aging is known to have deleterious effects on cerebral white matter, yet little is known about these white matter alterations in advanced age. In this study, 94 oldest-old adults without dementia (90-103 years) underwent diffusion tensor imaging to assess relationships between chronological age and multiple measures of integrity in 18 white matter regions across the brain. Results revealed significant age-related declines in integrity in regions previously identified as being sensitive to aging in younger-old adults (corpus callosum, fornix, cingulum, external capsule)...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28527524/c9orf72-hexanucleotide-repeat-expansions-and-ataxin-2-intermediate-length-repeat-expansions-in-indian-patients-with-amyotrophic-lateral-sclerosis
#7
Priyam Narain, James Gomes, Rohit Bhatia, Inder Singh, Perumal Vivekanandan
Repeat expansions in the chromosome 9 open reading frame 72 (C9orf72) gene have been recognized as a major contributor to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in the Caucasian population. Intermediate length repeat expansions of CAG (polyQ) repeat in the ATXN2 gene have also been reported to increase the risk of developing ALS in North America and Europe. We screened 131 ALS patients and 127 healthy controls from India for C9orf72 and ATXN2 repeat expansions. We found pathogenic hexanucleotide expansions in 3 of the 127 sporadic ALS patients, in 1 of the 4 familial ALS patients, and in none of the healthy controls...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28526294/central-amygdala-activation-of-extracellular-signal-regulated-kinase-1-and-age-dependent-changes-in-inflammatory-pain-sensitivity-in-mice
#8
Katelyn E Sadler, Nathan M Gartland, Jane E Cavanaugh, Benedict J Kolber
Aging populations are more sensitive to noxious stimuli as a result of altered somatosensory systems. In these experiments, we examined pain-like behaviors in young, middle-aged, and old mice during peripheral inflammation to determine if the same sensitivity exists in preclinical animal models. Immediately following injury, middle-aged and old mice exhibited more spontaneous pain-like behaviors than young mice, matching pain prevalence in clinical populations. Middle-aged and old mice also developed persistent mechanical hypersensitivity in the injured paw...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28526295/large-scale-exploratory-genetic-analysis-of-cognitive-impairment-in-parkinson-s-disease
#9
Ignacio F Mata, Catherine O Johnson, James B Leverenz, Daniel Weintraub, John Q Trojanowski, Vivianna M Van Deerlin, Beate Ritz, Rebecca Rausch, Stewart A Factor, Cathy Wood-Siverio, Joseph F Quinn, Kathryn A Chung, Amie L Peterson-Hiller, Alberto J Espay, Fredy J Revilla, Johnna Devoto, Dora Yearout, Shu-Ching Hu, Brenna A Cholerton, Thomas J Montine, Karen L Edwards, Cyrus P Zabetian
Cognitive impairment is a common and disabling problem in Parkinson's disease (PD). Identification of genetic variants that influence the presence or severity of cognitive deficits in PD might provide a clearer understanding of the pathophysiology underlying this important nonmotor feature. We genotyped 1105 PD patients from the PD Cognitive Genetics Consortium for 249,336 variants using the NeuroX array. Participants underwent assessments of learning and memory (Hopkins Verbal Learning Test-Revised [HVLT-R]), working memory/executive function (Letter-Number Sequencing and Trail Making Test [TMT] A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation [JoLO]), and global cognitive function (Montreal Cognitive Assessment)...
April 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28500878/identification-of-changes-in-neuronal-function-as-a-consequence-of-aging-and-tauopathic-neurodegeneration-using-a-novel-and-sensitive-magnetic-resonance-imaging-approach
#10
Sarah N Fontaine, Alexandria Ingram, Ryan A Cloyd, Shelby E Meier, Emily Miller, Danielle Lyons, Grant K Nation, Elizabeth Mechas, Blaine Weiss, Chiara Lanzillotta, Fabio Di Domenico, Frederick Schmitt, David K Powell, Moriel Vandsburger, Jose F Abisambra
Tauopathies, the most common of which is Alzheimer's disease (AD), constitute the most crippling neurodegenerative threat to our aging population. Tauopathic patients have significant cognitive decline accompanied by irreversible and severe brain atrophy, and it is thought that neuronal dysfunction begins years before diagnosis. Our current understanding of tauopathies has yielded promising therapeutic interventions but have all failed in clinical trials. This is partly due to the inability to identify and intervene in an effective therapeutic window early in the disease process...
April 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28499146/rna-sequencing-reveals-pronounced-changes-in-the-noncoding-transcriptome-of-aging-synaptosomes
#11
Bei Jun Chen, Uwe Ueberham, James D Mills, Ludmil Kirazov, Evgeni Kirazov, Mara Knobloch, Jana Bochmann, Renate Jendrek, Konii Takenaka, Nicola Bliim, Thomas Arendt, Michael Janitz
Normal aging is associated with impairments in cognitive functions. These alterations are caused by diminutive changes in the biology of synapses, and ineffective neurotransmission, rather than loss of neurons. Hitherto, only a few studies, exploring molecular mechanisms of healthy brain aging in higher vertebrates, utilized synaptosomal fractions to survey local changes in aging-related transcriptome dynamics. Here we present, for the first time, a comparative analysis of the synaptosomes transcriptome in the aging mouse brain using RNA sequencing...
April 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28494436/neuronal-tetraploidization-in-the-cerebral-cortex-correlates-with-reduced-cognition-in-mice-and-precedes-and-recapitulates-alzheimer-s-associated-neuropathology
#12
Noelia López-Sánchez, Ángela Fontán-Lozano, Anna Pallé, Valentina González-Álvarez, Alberto Rábano, José L Trejo, José M Frade
A controversy exists as to whether de novo-generated neuronal tetraploidy (dnNT) occurs in Alzheimer's disease. In addition, the presence of age-associated dnNT in the normal brain remains unexplored. Here we show that age-associated dnNT occurs in both superficial and deep layers of the cerebral cortex of adult mice, a process that is blocked in the absence of E2F1, a known regulator of cell cycle progression. This blockage correlates with improved cognition despite compromised neurogenesis in the adult hippocampus was confirmed in mice lacking the E2f1 gene...
April 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28482213/brain-predicted-age-in-down-syndrome-is-associated-with-beta-amyloid-deposition-and-cognitive-decline
#13
James H Cole, Tiina Annus, Liam R Wilson, Ridhaa Remtulla, Young T Hong, Tim D Fryer, Julio Acosta-Cabronero, Arturo Cardenas-Blanco, Robert Smith, David K Menon, Shahid H Zaman, Peter J Nestor, Anthony J Holland
Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer's disease-factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score...
April 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28482211/neuropsychological-measures-that-detect-early-impairment-and-decline-in-preclinical-alzheimer-disease
#14
Suzanne E Schindler, Mateusz S Jasielec, Hua Weng, Jason J Hassenstab, Ellen Grober, Lena M McCue, John C Morris, David M Holtzman, Chengjie Xiong, Anne M Fagan
Identifying which neuropsychological measures detect early cognitive changes associated with Alzheimer disease (AD), brain pathology would be helpful clinically for the diagnosis of early AD and for the design of clinical trials. We evaluated which neuropsychological measures in our cognitive battery are most strongly associated with cerebrospinal fluid (CSF) biomarkers of AD brain pathology. We studied a large cohort (n = 233) of middle-to older-aged community-dwelling individuals (mean age 61 years) who had no clinical symptoms of dementia and underwent baseline CSF collection at baseline...
April 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28532644/increasing-gaba-reverses-age-related-alterations-in-excitatory-receptive-fields-and-intensity-coding-of-auditory-midbrain-neurons%C3%A2-in%C3%A2-aged-mice
#15
Elliott J Brecht, Kathy Barsz, Benjamin Gross, Joseph P Walton
A key feature of age-related hearing loss is a reduction in the expression of inhibitory neurotransmitters in the central auditory system. This loss is partially responsible for changes in central auditory processing, as inhibitory receptive fields play a critical role in shaping neural responses to sound stimuli. Vigabatrin (VGB), an antiepileptic agent that irreversibly inhibits γ-amino butyric acid (GABA) transaminase, leads to increased availability of GABA throughout the brain. This study used multi-channel electrophysiology measurements to assess the excitatory frequency response areas in old CBA mice to which VGB had been administered...
April 12, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28478325/sirtuin-2-enhances-dopaminergic-differentiation-via-the-akt-gsk-3%C3%AE-%C3%AE-catenin-pathway
#16
Éva M Szegő, Ellen Gerhardt, Tiago F Outeiro
Proper and efficient differentiation of dopaminergic (DA) neurons is essential for the cell-based dopamine replacement strategies that have become an attractive therapeutical option in Parkinson's disease, a disorder typically known for the degeneration of the nigral DA neurons. Here, we established that the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 2 (SIRT2) interacts with protein kinase B, and, via the glycogen synthase kinase 3β/β-catenin pathway, modulates the differentiation of DA neurons...
April 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28482212/the-frequency-and-influence-of-dementia-risk-factors-in-prodromal-alzheimer-s-disease
#17
Isabelle Bos, Stephanie J Vos, Lutz Frölich, Johannes Kornhuber, Jens Wiltfang, Wolfgang Maier, Oliver Peters, Eckhart Rüther, Sebastiaan Engelborghs, Ellis Niemantsverdriet, Ellen Elisa De Roeck, Magda Tsolaki, Yvonne Freund-Levi, Peter Johannsen, Rik Vandenberghe, Alberto Lleó, Daniel Alcolea, Giovanni B Frisoni, Samantha Galluzzi, Flavio Nobili, Silvia Morbelli, Alexander Drzezga, Mira Didic, Bart N van Berckel, Eric Salmon, Christine Bastin, Solene Dauby, Isabel Santana, Inês Baldeiras, Alexandre de Mendonça, Dina Silva, Anders Wallin, Arto Nordlund, Preciosa M Coloma, Angelika Wientzek, Myriam Alexander, Gerald P Novak, Mark Forrest Gordon, Åsa K Wallin, Harald Hampel, Hilkka Soininen, Sanna-Kaisa Herukka, Philip Scheltens, Frans R Verhey, Pieter Jelle Visser
We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline...
April 8, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28478324/estrogen-enhances-hippocampal-gray-matter-volume-in-young-and-older-postmenopausal-women-a-prospective-dose-response-study
#18
Kimberly Albert, Jessica Hiscox, Brian Boyd, Julie Dumas, Warren Taylor, Paul Newhouse
Estrogen administration following menopause has been shown to support hippocampally mediated cognitive processes. A number of previous studies have examined the effect of estrogen on hippocampal structure to determine the mechanism underlying estrogen effects on hippocampal function. However, these studies have been largely observational and provided inconsistent results. We examined the effect of short-term estradiol administration on hippocampal gray-matter volume in a prospective study with multiple doses of estradiol (placebo, 1 mg, and 2 mg)...
April 8, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28464981/amyloid-precursor-protein-reduction-enhances-the-formation-of-neurofibrillary-tangles-in-a-mutant-tau-transgenic-mouse-model
#19
Virginie Vanden Dries, Virginie Stygelbout, Nathalie Pierrot, Zehra Yilmaz, Valérie Suain, Robert De Decker, Luc Buée, Jean-Noël Octave, Jean-Pierre Brion, Karelle Leroy
Alzheimer's disease is characterized by the presence of 2 neuropathological lesions: neurofibrillary tangles, composed of tau proteins which are highly phosphorylated and phosphorylated on uncommon sites, and amyloid plaques, containing the Aß peptides generated from the amyloid precursor protein (APP). Reduction of some APP proteolytic derivatives in Alzheimer's disease such as sAPPα fragment has been reported and sAPPα has been shown to affect tau phosphorylation. To investigate in vivo the effect of absence of APP protein and its fragments on tau phosphorylation and the formation of neurofibrillary tangles, we have generated mice deleted for APP gene and overexpressing a human mutant tau protein and developing neurofibrillary tangles (APPKOTg30 mice)...
April 5, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28457579/amyloidosis-and-neurodegeneration-result-in-distinct-structural-connectivity-patterns-in-mild-cognitive-impairment
#20
Thomas Jacquemont, Fabrizio De Vico Fallani, Anne Bertrand, Stéphane Epelbaum, Alexandre Routier, Bruno Dubois, Harald Hampel, Stanley Durrleman, Olivier Colliot
Alzheimer's disease (AD) is increasingly considered as a disconnection syndrome. Previous studies of the structural connectome in early AD stages have focused on mild cognitive impaired subjects (MCI), considering them as a homogeneous group. We studied 168 subjects from the Alzheimer's Disease Neuroimaging Initiative database (116 MCI and 52 cognitively normal subjects). Biomarker-based stratification using amyloid biomarkers (AV45 PET) and neurodegeneration biomarkers (MRI and FDG PET) led to 4 subgroups based on amyloid positivity (A+/-) and neurodegeneration positivity (N+/-): A-N-, A+N-, A-N+, and A+N+...
April 5, 2017: Neurobiology of Aging
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