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Neurobiology of Aging

Helena Soler, Jonatan Dorca-Arévalo, Marta González, Sara Esmeralda Rubio, Jesús Ávila, Eduardo Soriano, Marta Pascual
Alzheimer's disease (AD), the most common cause of dementia nowadays, has been linked to alterations in the septohippocampal pathway (SHP), among other circuits in the brain. In fact, the GABAergic component of the SHP, which controls hippocampal rhythmic activity crucial for learning and memory, is altered in the J20 mouse model of AD-a model that mimics the amyloid pathology of this disease. However, AD is characterized by another pathophysiological hallmark: the hyperphosphorylation and aggregation of the microtubule-associated protein Tau...
September 15, 2016: Neurobiology of Aging
Claudio Del Percio, Wilhelmus Drinkenburg, Susanna Lopez, Francesco Infarinato, Jesper Frank Bastlund, Bettina Laursen, Jan T Pedersen, Ditte Zerlang Christensen, Gianluigi Forloni, Angelisa Frasca, Francesco M Noè, Marina Bentivoglio, Paolo Francesco Fabene, Giuseppe Bertini, Valeria Colavito, Jonathan Kelley, Sophie Dix, Jill C Richardson, Claudio Babiloni
Resting state electroencephalographic (EEG) rhythms reflect the fluctuation of cortical arousal and vigilance in a typical clinical setting, namely the EEG recording for few minutes with eyes closed (i.e., passive condition) and eyes open (i.e., active condition). Can this procedure be back-translated to C57 (wild type) mice for aging studies? On-going EEG rhythms were recorded from a frontoparietal bipolar channel in 85 (19 females) C57 mice. Male mice were subdivided into 3 groups: 25 young (4.5-6 months), 18 middle-aged (12-15 months), and 23 old (20-24 months) mice to test the effect of aging...
September 15, 2016: Neurobiology of Aging
Namita A Padgaonkar, Theodore P Zanto, Jacob Bollinger, Adam Gazzaley
Older adults, compared to younger adults, do not benefit from predictive information regarding either what type of stimuli they will see or when to expect them, yet it is unclear whether older adults benefit when given both types of predictive information. Here, electroencephalogram recordings of older (aged 62-87 years) and younger (aged 20-32 years) adults were recorded during a working memory task. Each trial contained 2 faces and 2 scenes presented sequentially, followed by a 5-second delay and a probe stimulus...
September 13, 2016: Neurobiology of Aging
Jost-Julian Rumpf, Mirko Wegscheider, Karen Hinselmann, Christopher Fricke, Bradley R King, David Weise, Juliane Klann, Ferdinand Binkofski, Giovanni Buccino, Avi Karni, Julien Doyon, Joseph Classen
Consolidation, by which performance increments after a training intervention are secured and sometimes generated, is reduced in elderly humans. The present study addressed the question whether transcranial direct current stimulation (tDCS) applied after motor training improves consolidation of explicit motor sequence learning in healthy older humans. In the first experiment, anodal or cathodal tDCS to the left primary motor cortex, anodal tDCS to premotor cortex, or sham tDCS was applied immediately after completion of a finger sequence learning task...
September 13, 2016: Neurobiology of Aging
Timothy Rittman, Mikail Rubinov, Petra E Vértes, Ameera X Patel, Cedric E Ginestet, Boyd C P Ghosh, Roger A Barker, Maria Grazia Spillantini, Edward T Bullmore, James B Rowe
Abnormalities of tau protein are central to the pathogenesis of progressive supranuclear palsy, whereas haplotype variation of the tau gene MAPT influences the risk of Parkinson disease and Parkinson's disease dementia. We assessed whether regional MAPT expression might be associated with selective vulnerability of global brain networks to neurodegenerative pathology. Using task-free functional magnetic resonance imaging in progressive supranuclear palsy, Parkinson disease, and healthy subjects (n = 128), we examined functional brain networks and measured the connection strength between 471 gray matter regions...
September 9, 2016: Neurobiology of Aging
Maryam Ziaei, Hana Burianová, William von Hippel, Natalie C Ebner, Louise H Phillips, Julie D Henry
Normal adult aging is associated with difficulties in processing social cues to emotions such as anger and also altered motivation to focus more on positive than negative information. Gaze direction is an important modifier of the social signals conveyed by an emotion, for example, an angry face looking directly at you is considerably more threatening than an angry face looking away. In the present study we tested the hypothesis that older adults would show less neural differentiation to angry faces with direct and avert gaze compared to younger people, with the opposite prediction for happy faces...
September 6, 2016: Neurobiology of Aging
Gennady V Roshchupkin, Hieab H Adams, Sven J van der Lee, Meike W Vernooij, Cornelia M van Duijn, Andre G Uitterlinden, Aad van der Lugt, Albert Hofman, Wiro J Niessen, Mohammad A Ikram
The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions...
September 4, 2016: Neurobiology of Aging
Cinzia Costa, Lucilla Parnetti, Marcello D'Amelio, Alessandro Tozzi, Michela Tantucci, Andrea Romigi, Sabrina Siliquini, Virve Cavallucci, Massimiliano Di Filippo, Petra Mazzocchetti, Claudio Liguori, Annalisa Nobili, Paolo Eusebi, Nicola B Mercuri, Paolo Calabresi
Experimental and clinical observations indicate that amyloid-β1-42 (Aβ1-42) peptide not only represents a major actor in neurodegenerative mechanisms but also induce hyperexcitation in individual neurons and neural circuits. In this abnormal excitability, possibly leading to seizures, the D1 dopamine (DA) receptors may play a role. Cerebrospinal fluid levels of Aβ1-42 were measured in patients with late-onset epilepsy of unknown etiology. Moreover, the effect of amyloid peptide on the hippocampal epileptic threshold and synaptic plasticity and its link to D1 receptor function were tested in experimental mouse model of cerebral amyloidosis and in acute model of Aβ1-42-induced neurotoxicity...
September 3, 2016: Neurobiology of Aging
Celia Kun-Rodrigues, Owen A Ross, Tatiana Orme, Claire Shepherd, Laura Parkkinen, Lee Darwent, Dena Hernandez, Olaf Ansorge, Lorraine N Clark, Lawrence S Honig, Karen Marder, Afina Lemstra, Philippe Scheltens, Wiesje van der Flier, Eva Louwersheimer, Henne Holstege, Ekaterina Rogaeva, Peter St George-Hyslop, Elisabet Londos, Henrik Zetterberg, Imelda Barber, Anne Braae, Kristelle Brown, Kevin Morgan, Walter Maetzler, Daniela Berg, Claire Troakes, Safa Al-Sarraj, Tammaryn Lashley, Janice Holton, Yaroslau Compta, Vivianna Van Deerlin, John Q Trojanowski, Geidy E Serrano, Thomas G Beach, Jordi Clarimon, Alberto Lleó, Estrella Morenas-Rodríguez, Suzanne Lesage, Douglas Galasko, Eliezer Masliah, Isabel Santana, Monica Diez, Pau Pastor, Pentti J Tienari, Liisa Myllykangas, Minna Oinas, Tamas Revesz, Andrew Lees, Brad F Boeve, Ronald C Petersen, Tanis J Ferman, Valentina Escott-Price, Neill Graff-Radford, Nigel J Cairns, John C Morris, David J Stone, Stuart Pickering-Brown, David Mann, Dennis W Dickson, Glenda M Halliday, Andrew Singleton, Rita Guerreiro, Jose Bras
C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB...
September 2, 2016: Neurobiology of Aging
Simon J Schreiner, Thomas Kirchner, Michael Wyss, Jiri M G Van Bergen, Frances C Quevenco, Stefanie C Steininger, Erica Y Griffith, Irene Meier, Lars Michels, Anton F Gietl, Sandra E Leh, Adam M Brickman, Christoph Hock, Roger M Nitsch, Klaas P Pruessmann, Anke Henning, Paul G Unschuld
Low episodic memory performance characterizes elderly subjects at increased risk for Alzheimer's disease (AD) and may reflect neuronal dysfunction within the posterior cingulate cortex and precuneus (PCP) region. To investigate a potential association between cerebral neurometabolism and low episodic memory in the absence of cognitive impairment, tissue-specific magnetic resonance spectroscopic imaging at ultrahigh field strength of 7 Tesla was used to investigate the PCP region in a healthy elderly study population (n = 30, age 70 ± 5...
August 31, 2016: Neurobiology of Aging
Michael Craig, Thomas Wolbers, Mathew A Harris, Patrick Hauff, Sergio Della Sala, Michaela Dewar
Flexible spatial navigation depends on cognitive mapping, a function that declines with increasing age. In young adults, a brief period of postnavigation rest promotes the consolidation and integration of spatial memories into accurate cognitive maps. We examined (1) whether rest promotes spatial memory consolidation and integration in older adults; and (2) whether the magnitude of the rest benefit changes with increasing age. Young and older adults learned a route through a virtual environment, followed by a 10-minute delay comprising either wakeful rest or a perceptual task, and a subsequent cognitive mapping task, requiring the pointing to landmarks from different locations...
August 31, 2016: Neurobiology of Aging
Elyse Rosa, Sujeivan Mahendram, Yazi D Ke, Lars M Ittner, Stephen D Ginsberg, Margaret Fahnestock
In Alzheimer's disease, soluble tau accumulates and deposits as neurofibrillary tangles (NFTs). However, a precise toxic mechanism of tau is not well understood. We hypothesized that overexpression of wild-type tau downregulates brain-derived neurotrophic factor (BDNF), a neurotrophic peptide essential for learning and memory. Two transgenic mouse models of human tau expression and human tau (hTau40)-transfected human neuroblastoma (SH-SY5Y) cells were used to examine the effect of excess or pathologically modified wild-type human tau on BDNF expression...
August 31, 2016: Neurobiology of Aging
Claudio Babiloni, Claudio Del Percio, Anna Caroli, Elena Salvatore, Emanuele Nicolai, Nicola Marzano, Roberta Lizio, Enrica Cavedo, Susan Landau, Kewei Chen, William Jagust, Eric Reiman, Gioacchino Tedeschi, Patrizia Montella, Manuela De Stefano, Loreto Gesualdo, Giovanni B Frisoni, Andrea Soricelli
Cortical sources of resting state electroencephalographic (EEG) delta (2-4 Hz) and low-frequency alpha (8-10.5 Hz) rhythms show abnormal activity (i.e., current density) in patients with dementia due to Alzheimer's disease (AD). Here, we hypothesized that abnormality of this activity is related to relevant disease processes as revealed by cortical hypometabolism typically observed in AD patients by fluorodeoxyglucose positron emission tomography. Resting state eyes-closed EEG data were recorded in 19 AD patients with dementia and 40 healthy elderly (Nold) subjects...
August 31, 2016: Neurobiology of Aging
Philip S Insel, Michael C Donohue, R Scott Mackin, Paul S Aisen, Oskar Hansson, Michael W Weiner, Niklas Mattsson
Cognitively-normal people with evidence of β-amyloid (Aβ) pathology and subtle cognitive dysfunction are believed to be at high risk for progression to mild cognitive impairment due to Alzheimer's disease (AD). Clinical trials in later stages of AD typically include a coprimary endpoint to demonstrate efficacy on both cognitive and functional assessments. Recent trials focus on cognitively-normal people, but functional decline has not been explored for trial designs in this group. The goal of this study was therefore to characterize cognitive and functional decline in (1) cognitively-normal people converting to mild cognitive impairment (MCI) and (2) cognitively-normal β-amyloid-positive (Aβ+) people...
August 26, 2016: Neurobiology of Aging
Katharina Kolbe, Hassan Bukhari, Christina Loosse, Gregor Leonhardt, Annika Glotzbach, Magdalena Pawlas, Katharina Hess, Carsten Theiss, Thorsten Müller
Nuclear spheres are protein aggregates consisting of FE65, TIP60, BLM, and other yet unknown proteins. Generation of these structures in the cellular nucleus is putatively modulated by the amyloid precursor protein (APP), either by its cleavage or its phosphorylation. Nuclear spheres were preferentially studied in cell culture models and their existence in the human brain had not been known. Existence of nuclear spheres in the human brain was studied using immunohistochemistry. Cell culture experiments were used to study regulative mechanisms of nuclear sphere generation...
August 26, 2016: Neurobiology of Aging
Stephanie L Leal, Jessica A Noche, Elizabeth A Murray, Michael A Yassa
While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation...
August 25, 2016: Neurobiology of Aging
Claire Lancaster, Naji Tabet, Jennifer Rusted
Possession of an Apolipoprotein E (APOE) e4 allele is an established risk factor for Alzheimer's disease, whereas the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. Sixty-six volunteers, aged 45-55 years, completed 3 tasks that provided complementary measures of attentional control: prospective memory, sustained attention, and inhibition. Performance was compared between e2 carriers, e4 carriers, and e3 homozygotes (the population norm)...
August 25, 2016: Neurobiology of Aging
Elijah Mak, Sean J Colloby, Alan Thomas, John T O'Brien
Late-life depression (LLD) has been associated with both generalized and focal neuroanatomical changes including gray matter atrophy and white matter abnormalities. However, previous literature has not been consistent and, in particular, its impact on the topology organization of brain networks remains to be established. In this multimodal study, we first examined cortical thickness, and applied graph theory to investigate structural covariance networks in LLD. Thirty-three subjects with LLD and 25 controls underwent T1-weighted, fluid-attenuated inversion recovery and clinical assessments...
August 24, 2016: Neurobiology of Aging
Marino Coradazzi, Rosario Gulino, Francesco Fieramosca, Lucia Verga Falzacappa, Margherita Riggi, Giampiero Leanza
Noradrenergic neurons in the locus coeruleus play a role in learning and memory, and their loss is an early event in Alzheimer's disease pathogenesis. Moreover, noradrenaline may sustain hippocampal neurogenesis; however, whether are these events related is still unknown. Four to five weeks following the selective immunotoxic ablation of locus coeruleus neurons, young adult rats underwent reference and working memory tests, followed by postmortem quantitative morphological analyses to assess the extent of the lesion, as well as the effects on proliferation and/or survival of neural progenitors in the hippocampus...
August 24, 2016: Neurobiology of Aging
Julia A Scott, Meredith N Braskie, Duygu Tosun, Pauline Maillard, Paul M Thompson, Michael Weiner, Charles DeCarli, Owen T Carmichael
Cross-sectional studies show that elevated cerebral amyloid is associated with greater white-matter hyperintensity (WMH) burden in cognitively normal (CN) older adults. However, the relative time courses of amyloid and WMH accrual are unclear. To address this, we tested the associations between known WMH correlates-age, hypertension, and amyloid-with WMH accrual rate. We used brain magnetic resonance imaging to measure WMH change in 112 CN Alzheimer's Disease Neuroimaging Initiative (GO/2) participants over a 2-year period...
August 24, 2016: Neurobiology of Aging
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