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Neurobiology of Aging

Roberto Fontana, Mario Agostini, Emanuele Murana, Mufti Mahmud, Elena Scremin, Maria Rubega, Giovanni Sparacino, Stefano Vassanelli, Cristina Fasolato
Alterations of brain network activity are observable in Alzheimer's disease (AD) together with the occurrence of mild cognitive impairment, before overt pathology. However, in humans as well in AD mouse models, identification of early biomarkers of network dysfunction is still at its beginning. We performed in vivo recordings of local field potential activity in the dentate gyrus of PS2APP mice expressing the human amyloid precursor protein (APP) Swedish mutation and the presenilin-2 (PS2) N141I. From a frequency-domain analysis, we uncovered network hyper-synchronicity as early as 3 months, when intracellular accumulation of amyloid beta was also observable...
November 5, 2016: Neurobiology of Aging
A Starnawska, Q Tan, A Lenart, M McGue, O Mors, A D Børglum, K Christensen, M Nyegaard, L Christiansen
The epigenetic clock, also known as DNA methylation age (DNAmAge), represents age-related changes of DNA methylation at multiple sites of the genome and is suggested to be a biomarker for biological age. Elevated blood DNAmAge is associated with all-cause mortality, with the strongest effects reported in a recent intrapair twin study where epigenetically older twins had increased mortality risk in comparison to their co-twins. In the study presented here, we hypothesize that DNAmAge in blood is associated with cross-sectional and longitudinal cognitive abilities in middle-aged individuals...
November 4, 2016: Neurobiology of Aging
Takashi Matsushima, Silvio Conedera, Ryota Tanaka, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Aya Ikeda, Yuka Hosaka, Ayame Okuzumi, Yoshiaki Shimada, Kazuo Yamashiro, Yumiko Motoi, Kenya Nishioka, Nobutaka Hattori
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by cerebral infarction related to mutations in the notch homolog protein 3 (NOTCH3). We enrolled 10 patients whose brain magnetic resonance imaging (MRI) fluid-attenuated inversion recovery images showed hyperintensities (HIs) in the deep white matter and the external capsule. We then investigated the mutations in NOTCH3 using direct sequencing within the region of intron-exon boundaries in exons 2-24 of NOTCH3...
November 2, 2016: Neurobiology of Aging
Matthieu P Boisgontier, Boris Cheval, Sima Chalavi, Peter van Ruitenbeek, Inge Leunissen, Oron Levin, Alice Nieuwboer, Stephan P Swinnen
It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss...
November 1, 2016: Neurobiology of Aging
Thomas H Bak, Ian Robertson
The question of whether bilingualism can influence cognitive functions in healthy aging as well as in brain diseases is currently a topic of an intense debate. In a study published in this issue of the "Neurobiology of Ageing", Estanga et al. are breaking new ground by combining cognitive and biological approaches. Based on the data from the Guipuzkoa Alzheimer Project, they report that, compared with monolinguals, early bilinguals are not only characterized by a better cognitive performance in several domains and a lower prevalence of Alzheimer's disease but also by lower levels of t-tau in their cerebrospinal fluid...
October 21, 2016: Neurobiology of Aging
Monica Gagliardi, Grazia Iannello, Carmela Colica, Grazia Annesi, Aldo Quattrone
Parkinson's disease (PD) is the most common form of degenerative Parkinsonism with a prevalence of 1% of those older than 65 years. PD is characterized by the combination of slowness of movement (bradykinesia), muscular rigidity, resting tremor, and postural instability. Recently, using a genome-wide linkage analysis and exome sequencing, a group identified a candidate gene (CHCHD2) in a large Japanese family with autosomal dominant Parkinson's disease. The aim of this study was to evaluate the presence of CHCHD2 mutations in a cohort of 165 familial patients with clinically diagnosed PD and 200 control subjects from South Italy...
October 21, 2016: Neurobiology of Aging
Cristina Tejera-Parrado, Silvia Jesús, Ismael Huertas-Fernández, Inmaculada Bernal-Bernal, Marta Bonilla-Toribio, Isabel Córdoba-Tevar, Irene Abreu-Rodríguez, Fátima Carrillo, Maravilla Bernal-Escudero, Laura Vargas-González, Manuel Carballo, Pilar Gómez-Garre, Pablo Mir
Researching genetic factors involved in Parkinson's disease (PD) is crucial to increase our knowledge about the pathophysiology of the disorder. A missense mutation has recently been reported within CHCHD2, a gene newly associated with autosomal dominant PD. Subsequent studies in different ethnic populations have not reached any conclusive result about the role of CHCHD2 in PD. Therefore, the aim of this study was to investigate the implication of this gene for a PD population from southern Spain (including 536 PD patients and 518 unrelated control subjects)...
October 21, 2016: Neurobiology of Aging
Hsien-Han Lin, Ruey-Meei Wu, Han-I Lin, Meng-Ling Chen, Chun-Hwei Tai, Chin-Hsien Lin
Loss of function mutations in RAB39B were recently linked to X-linked recessive early-onset Parkinsonism with variable degrees of intellectual dysfunction. Postmortem examination of the brain biopsy from a patient carrying the gene deletion revealed widespread α-synuclein pathology. However, subsequent analyses reported conflict results to replicate the role of RAB39B mutations in patients with early-onset Parkinsonism. The aim of this study was to address the genetic contribution of RAB39B in early-onset and familial Parkinson's disease (PD) in a Taiwanese population...
October 21, 2016: Neurobiology of Aging
Yuyu Kunimura, Kinuyo Iwata, Akihito Ishigami, Hitoshi Ozawa
Pulsatile secretion of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) decreases during aging. Kisspeptin (encoded by Kiss1) neurons in the arcuate nucleus coexpress neurokinin B (Tac3) and dynorphin (Pdyn) and are critical for regulating the GnRH/LH pulse. We therefore examined kisspeptin neurons by histochemistry and pulsatile LH release in rats aged 2-3 (Young), 12-13 (Young-Middle), 19-22 (Late-Middle), and 24-26 (Old) months. Total LH concentrations, sampled for 3 hours, decreased in both sexes with aging...
October 19, 2016: Neurobiology of Aging
Petra Pasanen, Eino Palin, Risto Pohjolan-Pirhonen, Minna Pöyhönen, Juha O Rinne, Markku Päivärinta, Mika H Martikainen, Valtteri Kaasinen, Marja Hietala, Maria Gardberg, Anna Maija Saukkonen, Johanna Eerola-Rautio, Seppo Kaakkola, Jukka Lyytinen, Pentti J Tienari, Anders Paetau, Anu Suomalainen, Liisa Myllykangas
Mutations in SNCA are rare causes of familial Parkinson's disease (PD). We have previously described a novel p.Ala53Glu mutation in 2 Finnish families. To assess this mutation's frequency among Finnish PD patients, we screened 110 PD patients (mean age-of-onset 60 years) from Western Finland by Sanger sequencing of the third coding exon of SNCA. In addition, a sample of 47 PD subjects (mean age-of-onset 53 years) originating from Southern and Eastern Finland were studied using next-generation sequencing covering SNCA...
October 19, 2016: Neurobiology of Aging
Vincent Maingret, Gaël Barthet, Séverine Deforges, Nan Jiang, Christophe Mulle, Thierry Amédée
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by early cognitive deficits linked to synaptic dysfunction and loss. Considerable evidence suggests that neuroinflammation contributes to AD. Prostaglandin E2 (PGE2), a key neuroinflammatory molecule, modulates hippocampal synaptic transmission and plasticity. We investigated the effect of PGE2 on synaptic transmission and presynaptic plasticity at synapses between mossy fibers from the dentate gyrus and CA3 pyramidal cells (Mf-CA3 synapse)...
October 17, 2016: Neurobiology of Aging
Darren R Hocking, Rachael C Birch, Quang M Bui, Jasmine C Menant, Stephen R Lord, Nellie Georgiou-Karistianis, David E Godler, Wei Wen, Anna Hackett, Carolyn Rogers, Julian N Trollor
Recent evidence indicates that adults with a premutation (PM: 55-199 CGG repeats) expansion in the fragile X mental retardation 1 (FMR1) gene show postural control deficits that may reflect disruption to cerebellar motor regions. Less is known about the influence of reduced cerebellar volume and structural changes, and increase in CGG repeat and FMR1 mRNA levels on the attentional demands of step initiation in PM males. We investigated the effects of a concurrent cognitive task on choice stepping reaction time (CSRT) and explored the associations between CSRT performance, cerebellar volume, CGG size, and FMR1 mRNA levels in blood in PM males...
October 15, 2016: Neurobiology of Aging
Selva L Luna, Donald I Brown, Dominique H Eghlidi, Steven G Kohama, Henryk F Urbanski
Reduced activity has been linked to age-associated physiological changes but the underlying root cause is unclear. The goal of the present study was to compare the orexin neuronal system of old (23-29 years) female rhesus macaques with either active or sedentary 24-hour locomotor activity patterns. Using immunohistochemistry, we counted the number of orexin A and orexin B neurons in the lateral hypothalamic area of each animal. Overall, we observed no difference in the distribution pattern or number of either orexin A or orexin B immune-positive neurons between animals in the 2 groups...
October 15, 2016: Neurobiology of Aging
Yihong Zhan, Honghua Zheng, Chen Wang, Zhouyi Rong, Naian Xiao, Qilin Ma, Yun-Wu Zhang
A subset of Alzheimer's disease (AD) occurrence shows autosomal dominant, familial inheritance patterns. Such familial AD (FAD) are caused by mutations in APP, PSEN1, and PSEN2 genes, which encode amyloid-β (Aβ) precursor protein, presenilin 1 (PS1), and presenilin 2 (PS2), respectively. Here, we report a novel PSEN1 mutation (c.1164C > G, p.F388L, mutation nomenclature according to National Center for Biotechnology Information Reference Sequence: NM_000021.3) occurring in a Chinese family with early-onset AD and cosegregating with affected family members...
October 15, 2016: Neurobiology of Aging
Catharina Zich, Stefan Debener, Ann-Kathrin Thoene, Ling-Chia Chen, Cornelia Kranczioch
Stroke frequently results in motor impairment. Motor imagery (MI), the mental practice of movements, has been suggested as a promising complement to other therapeutic approaches facilitating motor rehabilitation. Of particular potential is the combination of MI with neurofeedback (NF). However, MI NF protocols have been largely optimized only in younger healthy adults, although strokes occur more frequently in older adults. The present study examined the influence of age on the neural correlates of MI supported by electroencephalogram (EEG)-based NF and on the neural correlates of motor execution...
October 15, 2016: Neurobiology of Aging
Yat-Fung Shea, Angel On-Kei Chan, Leung-Wing Chu, Shui-Ching Lee, Chun-Yin Law, Chung-Him See, Kit-Ling Yiu, Patrick Ka-Chun Chiu
Autosomal dominant familial Alzheimer's disease accounts for 0.5% of all Alzheimer's disease. A familial Alzheimer's disease Chinese family, with 7 affected family members, underwent PSEN1 screening in 3 affected family members. A heterozygous novel missense mutation in the PSEN1 gene c.1156T>A, altering phenylalanine to isoleucine at codon 386, was identified. Because the change occurred in conserved domains of this gene and cosegregated with affected family members, this change may have a mutagenic and probably pathogenic effect...
October 15, 2016: Neurobiology of Aging
Joseph Webb, Auriel A Willette
Novel single nucleotide polymorphisms within Parkinson's disease (PD) can predict disease risk, but their influence on clinical, cognitive, and neurobiological indices remains unexplored. We investigated differences between functional polymorphisms at RS11158026 coding for guanosine triphosphate cyclohydrolase-1 (GCH1), an essential enzyme for dopamine production in nigrostriatal cells. Among newly diagnosed, untreated PD subjects and age-matched controls from the Parkinson's Progression Markers Initiative, T allele carriers showed higher PD risk (odds ratio = 1...
October 13, 2016: Neurobiology of Aging
Ziv Gan-Or, Jacques Y Montplaisir, Jay P Ross, Judes Poirier, Simon C Warby, Isabelle Arnulf, Stephanie Strong, Yves Dauvilliers, Claire S Leblond, Michele T M Hu, Birgit Högl, Ambra Stefani, Christelle Charley Monaca, Valérie Cochen De Cock, Michel Boivin, Luigi Ferini-Strambi, Giuseppe Plazzi, Elena Antelmi, Peter Young, Anna Heidbreder, Thomas R Barber, Samuel G Evetts, Michal Rolinski, Patrick A Dion, Alex Desautels, Jean-François Gagnon, Nicolas Dupré, Ronald B Postuma, Guy A Rouleau
The present study aimed to examine whether the APOE ε4 allele, associated with dementia with Lewy bodies (DLB), and possibly with dementia in Parkinson's disease (PD), is also associated with idiopathic rapid eye movement sleep behavior disorder (RBD). Two single nucleotide polymorphisms, rs429358 and rs7412, were genotyped in RBD patients (n = 480) and in controls (n = 823). APOE ε4 allele frequency was 0.14 among RBD patients and 0.13 among controls (OR = 1.11, 95% CI: 0.88-1.40, p = 0.41). APOE ε4 allele frequencies were similar in those who converted to DLB (0...
October 13, 2016: Neurobiology of Aging
Marine Tournissac, Milène Vandal, Arnaud François, Emmanuel Planel, Frédéric Calon
Thermoregulatory deficits coincide with a rise in the incidence of Alzheimer's disease (AD) in old age. Lower body temperature increases tau phosphorylation, a neuropathological hallmark of AD. To determine whether old age potentiates cold-induced tau phosphorylation, we compared the effects of cold exposure (4 °C, 24 hours) in 6- and 18-month-old mice. Cold-induced changes in body temperature, brown adipose tissue activity, and phosphorylation of tau at Ser202 were not different between 6- and 18-month-old mice...
October 12, 2016: Neurobiology of Aging
Thomas Gattringer, Michael Khalil, Christian Langkammer, Daniela Pinter, Stefan Ropele, Franz Fazekas, Christian Enzinger
No abstract text is available yet for this article.
October 11, 2016: Neurobiology of Aging
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