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Neurobiology of Aging

Miles Flitton, Nicholas Rielly, Rhian Warman, Donald Warden, A David Smith, Ian A Macdonald, Helen Miranda Knight
Low homocysteine levels and B vitamin treatment are reported to protect against declining cognitive health. Both B vitamins and homocysteine are involved in the production of S-adenosylmethionine, a universal methyl donor essential for the process of DNA methylation. We investigated the effect of a damaging coding variant within the DNA methyltransferase gene DNMT3L (R278G, A/G) by examining B vitamin intake, homocysteine levels, cognitive performance, and brain atrophy in individuals in the VITACOG study of mild cognitive impairment and the TwinsUK cohort...
February 13, 2019: Neurobiology of Aging
Giulia Gaggioni, Julien Q M Ly, Vincenzo Muto, Sarah L Chellappa, Mathieu Jaspar, Christelle Meyer, Tillo Delfosse, Amaury Vanvinckenroye, Romain Dumont, Dorothée Coppieters 't Wallant, Christian Berthomier, Justinas Narbutas, Maxime Van Egroo, Andé Luxen, Eric Salmon, Fabienne Collette, Christophe Phillips, Christina Schmidt, Gilles Vandewalle
Cortical excitability depends on sleep-wake regulation, is central to cognition, and has been implicated in age-related cognitive decline. The dynamics of cortical excitability during prolonged wakefulness in aging are unknown, however. Here, we repeatedly probed cortical excitability of the frontal cortex using transcranial magnetic stimulation and electroencephalography in 13 young and 12 older healthy participants during sleep deprivation. Although overall cortical excitability did not differ between age groups, the magnitude of cortical excitability variations during prolonged wakefulness was dampened in older individuals...
February 13, 2019: Neurobiology of Aging
Meaghan Elizabeth Spedden, Julia T Choi, Jens Bo Nielsen, Svend Sparre Geertsen
We investigated age-related differences in corticospinal control of muscle activity during normal and visually guided (VG) walking. Young (n = 15, 22.1 ± 1.7 years) and older (n = 15, 68.3 ± 2.7 years) participants performed normal walking and VG walking requiring precise foot placement based on visual cues. Coherence analysis was used to quantify coupling between electroencephalography and electromyography from the anterior tibial muscle (corticomuscular) and between the 2 ends of the anterior tibial muscle (intramuscular) at 15-50 Hz during the swing phase of walking as markers of corticospinal activity...
February 13, 2019: Neurobiology of Aging
Chen-Ye Zeng, Ting-Ting Yang, Hong-Jing Zhou, Yue Zhao, Xi Kuang, Wei Duan, Jun-Rong Du
Alzheimer's disease (AD) is the most common type of senile dementia. The antiaging gene Klotho is reported to decline in the brain of patients and animals with AD. However, the role of Klotho in the progression of AD remains elusive. The present study explored the effects and underlying mechanism of Klotho in a mouse model of AD. The upregulation of cerebral Klotho expression was mediated by an intracerebroventricular injection of a lentiviral vector that encoded Klotho (LV-KL) in 7-month-old amyloid precursor protein/presenilin 1 transgenic mice...
February 13, 2019: Neurobiology of Aging
Margherita Grasso, Paola Piscopo, Giuseppina Talarico, Leonardo Ricci, Alessio Crestini, Giuseppe Tosto, Marina Gasparini, Giuseppe Bruno, Michela A Denti, Annamaria Confaloni
The purpose of this study was to develop an easy and minimally invasive assay to detect a plasma miRNA profile in frontotemporal dementia (FTD) patients, with the final aim of discriminating between FTD patients and healthy controls (HCs). After a global miRNA profiling, significant downregulation of miR-663a, miR-502-3p, and miR-206 (p = 0.0001, p = 0.0002, and p = 0.02 respectively) in FTD patients was confirmed when compared with HCs in a larger case-control sample. Moreover, miR-663a and miR-502-3p showed significant differences in both genders, whereas miR-206, only in male subjects...
February 5, 2019: Neurobiology of Aging
Jack A Curran, Edgar Buhl, Krasimira Tsaneva-Atanasova, James J L Hodge
Aging has significant effects on circadian behavior across a wide variety of species, but the underlying mechanisms are poorly understood. Previous work has demonstrated the age-dependent decline in behavioral output in the model organism Drosophila. We demonstrate that this age-dependent decline in circadian output is combined with changes in daily activity of Drosophila. Aging also has a large impact on sleep behavior, significantly increasing sleep duration while reducing latency. We used electrophysiology to record from large ventral lateral neurons of the Drosophila circadian clock, finding a significant decrease in input resistance with age but no significant changes in spontaneous electrical activity or membrane potential...
February 2, 2019: Neurobiology of Aging
Rand S Eid, Jessica A Chaiton, Stephanie E Lieblich, Tamara S Bodnar, Joanne Weinberg, Liisa A M Galea
The maternal brain displays considerable plasticity, and motherhood is associated with changes in affective and cognitive function. Motherhood can alter the trajectory of brain aging, including modifications to neuroplasticity and cognition. Here, we investigated the short- and long-term effects of motherhood on hippocampal neurogenesis, microglial density and morphology, and circulating cytokines, domains known to be altered with age and implicated in cognition and mood. Female rats were bred then euthanized during gestation or at various postpartum time points, culminating in middle age, and nulliparous rats served as age-matched controls...
February 2, 2019: Neurobiology of Aging
Elaine Guo Yan Chew, Louis C S Tan, Wing-Lok Au, Kumar-M Prakash, Jianjun Liu, Jia Nee Foo, Eng-King Tan
A recent meta-analysis of Parkinson's disease (PD) genome-wide association studies has identified 17 novel risk loci in the European population. We aim to assess if these reported novel risk loci are similarly implicated in PD risk within the East Asian population by analyzing the reported risk single nucleotide polymorphism or proxy single nucleotide polymorphism in 14,006 East Asian samples (779 patients and 13,227 controls). We found that 9 of the 17 reported novel PD risk loci showed very similar effects in Europeans and East Asians (I2  = 0 to 10...
February 2, 2019: Neurobiology of Aging
Ying Gao, Ru-Jing Ren, Zi-Lin Zhong, Eric Dammer, Qian-Hua Zhao, Shan Shan, Zheng Zhou, Xia Li, Yue-Qi Zhang, Hai-Lun Cui, Yong-Bo Hu, Sheng-Di Chen, Jian-Jun Chen, Qi-Hao Guo, Gang Wang
Causative mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) account for a majority of cases of familial Alzheimer disease (FAD) inherited in an autosomal-dominant pattern. For the sake of characterizing mutations, index patients from 148 families with FAD were enrolled from mainland China. Sanger sequencing of the genes APP, PSEN1, and PSEN2 was performed to characterize the mutation spectrum of the Chinese population. Thirteen of 148 (8.8%) individuals had possible pathogenic APP, PSEN1, or PSEN2 variants, including 2 (15...
January 31, 2019: Neurobiology of Aging
Clémence Tomadesso, Julie Gonneaud, Stéphanie Egret, Audrey Perrotin, Alice Pélerin, Robin de Flores, Vincent de la Sayette, Béatrice Desgranges, Gaël Chételat, Renaud La Joie
Amnestic mild cognitive impairment (aMCI) is a clinical entity with various potential etiologies including but not limited to Alzheimer's disease. We examined whether a positive ([18F]Florbetapir) beta amyloid positron emission tomography scan, supporting underlying Alzheimer's disease pathophysiology, was associated with specific memory deficits in 48 patients with aMCI (33 beta amyloid positive, 15 beta amyloid negative). Memory was evaluated using an autobiographical fluency task and a word-list learning task with 2 different encoding types (shallow/incidental versus deep/intentional)...
January 31, 2019: Neurobiology of Aging
Nazanin Makkinejad, Julie A Schneider, Junxiao Yu, Sue E Leurgans, Aikaterini Kotrotsou, Arnold M Evia, David A Bennett, Konstantinos Arfanakis
Transactive response DNA-binding protein 43 (TDP-43) pathology is common in old age and is strongly associated with cognitive decline and dementia above and beyond contributions from other neuropathologies. TDP-43 pathology in aging typically originates in the amygdala, a brain region also affected by other age-related neuropathologies such as Alzheimer's pathology. The purpose of this study was two-fold: to determine the independent effects of TDP-43 pathology on the volume, as well as shape, of the amygdala in a community cohort of older adults, and to determine the contribution of amygdala volume to the variance of the rate of cognitive decline after accounting for the contributions of neuropathologies and demographics...
January 31, 2019: Neurobiology of Aging
Marina Dukhinova, Tatyana Veremeyko, Amanda W Y Yung, Inna S Kuznetsova, Thomas Y B Lau, Ekaterina Kopeikina, Andrew M L Chan, Eugene D Ponomarev
Although it was suggested that gangliosides play an important role in the binding of amyloid fragments to neuronal cells, the exact role of gangliosides in Alzheimer's disease (AD) pathology remains unclear. To understand the role of gangliosides in AD pathology in vivo, we crossed st3gal5-deficient (ST3-/- ) mice that lack major brain gangliosides GM1, GD1a, GD3, GT1b, and GQ1b with 5XFAD transgenic mice that overexpress 3 mutant human amyloid proteins AP695 and 2 presenilin PS1 genes. We found that ST3-/- 5XFAD mice have a significantly reduced burden of amyloid depositions, low level of neuroinflammation, and did not exhibit neuronal loss or synaptic dysfunction...
January 30, 2019: Neurobiology of Aging
Miao Sun, Chengyu Huang, Hui Wang, Huaye Zhang
The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Par3 forms a complex with BACE1 through its first PDZ domain, which is important for regulating BACE1 endosome-to-TGN trafficking...
January 30, 2019: Neurobiology of Aging
Zahra Jafari, Megan Okuma, Hadil Karem, Jogender Mehla, Bryan E Kolb, Majid H Mohajerani
Environmental distresses occurring during the sensitive periods of early life may exacerbate the vulnerability to develop physical and mental diseases in old age. Studies have shown the impact of prenatal stress (PS) on the endocrine development and reprogramming of hypothalamic-pituitary-adrenal axis functions in association with cognitive development and susceptibility to neuropsychiatric diseases. Long-term exposure to glucocorticoids can damage the brain and intensify the progression of Alzheimer's disease (AD)-like neuropathological changes, especially in females...
January 30, 2019: Neurobiology of Aging
Marilyn Horta, Maryam Ziaei, Tian Lin, Eric C Porges, Håkan Fischer, David Feifel, R Nathan Spreng, Natalie C Ebner
Aging is associated with increased difficulty in facial emotion identification, possibly due to age-related network change. The neuropeptide oxytocin (OT) facilitates emotion identification, but this is understudied in aging. To determine the effects of OT on dynamic facial emotion identification across adulthood, 46 young and 48 older participants self-administered intranasal OT or a placebo in a randomized, double-blind procedure. Older participants were slower and less accurate in identifying emotions. Although there was no behavioral treatment effect, partial least squares analysis supported treatment effects on brain patterns during emotion identification that varied by age and emotion...
January 29, 2019: Neurobiology of Aging
Tsz Hang Wong, Harro Seelaar, Shamiram Melhem, Annemieke J M Rozemuller, John C van Swieten
Mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) are major genetic causes of early-onset Alzheimer's disease (EOAD). Clinical heterogeneity is frequently observed in patients with PSEN1 and PSEN2 mutations. Using whole exome sequencing, we screened a Dutch cohort of 68 patients with EOAD for rare variants in Mendelian Alzheimer's disease, frontotemporal dementia, and prion disease genes. We identified 3 PSEN1 and 2 PSEN2 variants. Three variants, 1 in PSEN1 (p.H21Profs*2) and both PSEN2 (p...
January 29, 2019: Neurobiology of Aging
Arjan Blokland, Marlies A Van Duinen, Anke Sambeth, Pim R A Heckman, Max Tsai, Gezim Lahu, Tolga Uz, Jos Prickaerts
There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast administration (100, 250, 1000 μg) in a double-blind, placebo-controlled, 4-way crossover design. Participants were first screened for their verbal word memory performance to ensure normal memory performance (within 0...
January 26, 2019: Neurobiology of Aging
Michael R Milne, Lei Qian, Marion T Turnbull, Genevieve Kinna, Brett M Collins, Rohan D Teasdale, Elizabeth J Coulson
There is in vitro evidence that sorting nexin family member 27 (SNX27), a member of the retromer complex, changes the distribution of the amyloid-beta (Aβ) precursor protein (APP) to promote its recycling and thereby prevent the production of Aβ, the toxic protein associated with Alzheimer's disease (AD). In this study, we analyzed the phenotype of the familial AD APP/PS mouse strain lacking one copy of the SNX27 gene. The reduction in SNX27 expression had no significant effect on the in vivo accumulation of soluble, total, or plaque-deposited Aβ, which is overproduced by the familial APP/PS transgenes...
January 25, 2019: Neurobiology of Aging
Xiantao Li, Yimin Sun, Lingyun Gong, Li Zheng, Keliang Chen, Yan Zhou, Yuehua Gu, Yao Xu, Qihao Guo, Zhen Hong, Ding Ding, Jianhui Fu, Qianhua Zhao
Variants in triggering receptor expressed on myeloid cells 2 (TREM2) are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease. TREM2 homozygous mutations cause Nasu-Hakola disease, an early-onset recessive form of dementia preceded by bone cysts and fractures. The same type of mutations has been shown to cause frontotemporal dementia without the presence of any bone phenotype. Herein, we report a Chinese Han consanguineous family carrying a novel TREM2 mutation, presenting with early-onset dementia similar to behavioral variant frontotemporal dementia with mild radiological bone involvement...
January 24, 2019: Neurobiology of Aging
Claudio Babiloni, Claudio Del Percio, Maria Teresa Pascarelli, Roberta Lizio, Giuseppe Noce, Susanna Lopez, Marco Rizzo, Raffaele Ferri, Andrea Soricelli, Flavio Nobili, Dario Arnaldi, Francesco Famà, Francesco Orzi, Carla Buttinelli, Franco Giubilei, Marco Salvetti, Virginia Cipollini, Raffaella Franciotti, Marco Onofrj, Paola Stirpe, Peter Fuhr, Ute Gschwandtner, Gerhard Ransmayr, Dag Aarsland, Lucilla Parnetti, Lucia Farotti, Moira Marizzoni, Fabrizia D'Antonio, Carlo De Lena, Bahar Güntekin, Lutfu Hanoğlu, Görsev Yener, Derya Durusu Emek-Savaş, Antonio Ivano Triggiani, John Paul Taylor, Ian McKeith, Fabrizio Stocchi, Laura Vacca, Harald Hampel, Giovanni B Frisoni, Maria Francesca De Pandis, Laura Bonanni
Previous evidence has shown different resting-state eyes-closed electroencephalographic delta (<4 Hz) and alpha (8-10.5 Hz) source connectivity in subjects with dementia due to Alzheimer's (ADD) and Lewy body (DLB) diseases. The present study tested if the same differences may be observed in the prodromal stages of mild cognitive impairment (MCI). Here, clinical and resting-state eyes-closed electroencephalographic data in age-, gender-, and education-matched 30 ADMCI, 23 DLBMCI, and 30 healthy elderly (Nold) subjects were available in our international archive...
January 24, 2019: Neurobiology of Aging
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