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Neurobiology of Aging

Theresa M Harrison, Anne Maass, Suzanne L Baker, William J Jagust
The mechanisms underlying superior cognitive performance in some older adults are poorly understood. We used a multimodal approach to characterize imaging and cognitive features of 26 successful agers (SA; defined by superior episodic memory ability) and 103 typical older adults. Cortical thickness was greater in multiple regions in SA including right anterior cingulate and prefrontal cortex and was related to baseline memory performance. Similarly, hippocampal volume was greater in SA and associated with baseline memory...
March 27, 2018: Neurobiology of Aging
Sheng-Dan Nie, Xin Li, Can-E Tang, Fang-Yuan Min, Xia-Jie Shi, Liang-Yan Wu, Shan-Lei Zhou, Zi Chen, Jing Wu, Tao Song, Zhi-Jie Dai, Jiao Zheng, Jia-Jia Liu, Shan Wang
High glucose (HG)-induced mammalian target of rapamycin (mTOR) overactivation acts as a signaling hub for the formation of tau hyperphosphorylation, which contributes to the development of diabetes-associated cognitive deficit. How HG induces the sustained activation of mTOR in neurons is not clearly understood. ErbB4, a member of the receptor tyrosine kinase family, plays critical roles in development and function of neural circuitry, relevant to behavioral deficits. Here, we showed HG-induced ErbB4 overexpression in differentiated SH-SY5Y cells and primary hippocampal neurons and hippocampal pyramidal neurons of streptozotocin-induced diabetic rats...
March 23, 2018: Neurobiology of Aging
Young-Eun Kim, Ki-Wook Oh, Min-Young Noh, Jinseok Park, Hee-Jung Kim, Jong Eun Park, Chang-Seok Ki, Seung Hyun Kim
ATXN2 intermediate-length trinucleotide repeat expansions have been reported as a risk factor for amyotrophic lateral sclerosis (ALS) in various ethnicities. We tried to confirm this finding in Korean patients with ALS by screening ATXN2 cytosine-adenine-guanine nucleotide sequences (CAG) repeat lengths in 464 unrelated ALS patients and 703 controls. The most common and the highest CAG repeat lengths in the controls were 22 and 28, respectively, whereas those in ALS patients were 22 and 33, respectively. The frequency of CAG repeat lengths of 30 or more was significantly different between the 2 groups after Bonferroni correction (1...
March 23, 2018: Neurobiology of Aging
XiaoJing Gu, YongPing Chen, QingQing Zhou, Ying-Che Lu, Bei Cao, LingYu Zhang, Ming-Che Kuo, Yih-Ru Wu, Ruey-Meei Wu, Eng-King Tan, Hui-Fang Shang
A recent genome-wide association study performed in European population identified 4 potentially interesting gene loci of multiple system atrophy (MSA), including the EDN1 rs16872704, MAPT rs9303521, FBXO47 rs78523330, and ELOVL7 rs7715147. Because of the genetic heterogeneity, we aimed to explore the possible genetic association between above 4 single nucleotide polymorphisms (SNPs) and MSA in Chinese Han population from Mainland China, Taiwan, and Singapore. A total of 1847 subjects comprising 906 MSA patients and 941 unrelated healthy controls were genotyped by directly sequencing for these SNPs...
March 23, 2018: Neurobiology of Aging
Christine M Dengler-Crish, Hope C Ball, Li Lin, Kimberly M Novak, Lisa Noelle Cooper
Low bone mineral density (BMD) is a significant comorbidity in Alzheimer's disease (AD) and may reflect systemic regulatory pathway dysfunction. Low BMD has been identified in several AD mouse models selective for amyloid-β or tau pathology, but these deficits were attributed to diverse mechanisms. In this study, we identified common pathophysiological mechanisms accounting for bone loss and neurodegeneration in the htau mouse, a tauopathy model with an early low BMD phenotype. We investigated the Wnt/β-catenin pathway-a cellular signaling cascade linked to both bone loss and neuropathology...
March 23, 2018: Neurobiology of Aging
Kajri A Sheth, Chitra C Iyer, Christopher G Wier, Alexander E Crum, Anna Bratasz, Stephen J Kolb, Brian C Clark, Arthur H M Burghes, W David Arnold
In older adults, the loss of muscle strength (dynapenia) and the loss of muscle mass (sarcopenia) are important contributors to the loss of physical function. We sought to investigate dynapenia, sarcopenia, and the loss of motor unit function in aging mice. C57BL/6J mice were analyzed with cross-sectional (males: 3 vs. 27 months; males and females: 8 vs. 12 vs. 20 months) and longitudinal studies (males: 10-25 months) using in vivo electrophysiological measures of motor unit connectivity (triceps surae compound muscle action potential and motor unit number estimation), in vivo measures of plantar flexion torque, magnetic resonance imaging of hind limb muscle volume, and grip strength...
March 23, 2018: Neurobiology of Aging
Mahendra Singh, Pedro Miura, Robert Renden
Hearing acuity and sound localization are affected by aging and may contribute to cognitive dementias. Although loss of sensorineural conduction is well documented to occur with age, little is known regarding short-term synaptic plasticity in central auditory nuclei. Age-related changes in synaptic transmission properties were evaluated at the mouse calyx of Held, a sign-inverting relay synapse in the circuit for sound localization, in juvenile adults (1 month old) and late middle-aged (18-21 months old) mice...
March 21, 2018: Neurobiology of Aging
Andrei G Vlassenko, Brian A Gordon, Manu S Goyal, Yi Su, Tyler M Blazey, Tony J Durbin, Lars E Couture, Jon J Christensen, Hussain Jafri, John C Morris, Marcus E Raichle, Tammie L-S Benzinger
Research of the human brain metabolism in vivo has largely focused on total glucose use (via fluorodeoxyglucose positron emission tomography) and, until recently, did not examine the use of glucose outside oxidative phosphorylation, which is known as aerobic glycolysis (AG). AG supports important functions including biosynthesis and neuroprotection but decreases dramatically with aging. This multitracer positron emission tomography study evaluated the relationship between AG, total glucose use (CMRGlc), oxygen metabolism (CMRO2 ), tau, and amyloid deposition in 42 individuals, including those at preclinical and symptomatic stages of Alzheimer's disease...
March 20, 2018: Neurobiology of Aging
Chao Wu, Wei-Gang Gong, Yan-Juan Wang, Jun-Jun Sun, Hong Zhou, Zhi-Jun Zhang, Qing-Guo Ren
Chronic stress, a causal factor for depression, can also cause cognitive impairments and tau pathology. However, whether and how the selective serotonin reuptake inhibitor antidepressant escitalopram ameliorates these effects are still unclear. In the present study, rats were subjected to chronic mild unpredictable stress for 8 weeks. Following the initial 4 weeks, the stressed animals were separated into susceptible (depressive) and unsusceptible (resistant) groups based on behavioral tests. Then, escitalopram (10 mg/kg i...
March 19, 2018: Neurobiology of Aging
Chu-Chung Huang, Albert C Yang, Kun-Hsien Chou, Mu-En Liu, Shih-Chun Fang, Chi-Chang Chen, Shih-Jen Tsai, Ching-Po Lin
White matter hyperintensities (WMHs) are prevalent in the older adult and are often accompanied by cognitive decline and an increased risk of dementia. However, the roles of WMHs in the periventricular white matter and deep white matter regions in the aging process remain controversial. This study aimed to investigate the WMH burden across the adult lifespan and determine the interrelationships among age, WMH, and cognition. The present study included 312 healthy individuals aged 21-89 years who received structural magnetic resonance imaging and cognitive assessments...
March 19, 2018: Neurobiology of Aging
Meenakshi Dauwan, Mascha M J Linszen, Afina W Lemstra, Philip Scheltens, Cornelis J Stam, Iris E Sommer
We studied neurophysiological indicators of hallucinations in Alzheimer's disease patients with hallucinations (ADhall+), and compared them with nonhallucinating AD (ADhall-) and dementia with Lewy bodies (DLBhall+) patients. Thirty-six matched ADhall+ and 108 ADhall- and 29 DLBhall+ patients were selected from the Amsterdam Dementia Cohort. Electroencephalography (EEG) spectral and functional connectivity (FC) analyses (phase lag index) were performed. Quantitative and visual EEG measures were combined in a random forest algorithm to determine which EEG-based variable(s) play a role in hallucinations...
March 19, 2018: Neurobiology of Aging
Robert S Wilson, Ana W Capuano, Lei Yu, Jingyun Yang, Namhee Kim, Sue E Leurgans, Melissa Lamar, Julie A Schneider, David A Bennett, Patricia A Boyle
Retest learning impacts estimates of cognitive aging, but its bases are uncertain. Here, we test the hypothesis that dementia-related neurodegeneration impairs retest learning. Older persons without cognitive impairment at enrollment (n = 567) had annual cognitive testing for a mean of 11 years, died, and had a neuropathologic examination to quantify 5 neurodegenerative pathologies. Change point models were used to divide cognitive trajectories into an early retest sensitive component and a later component less sensitive to retest...
March 17, 2018: Neurobiology of Aging
Niran Hadad, Archana Unnikrishnan, Jordan A Jackson, Dustin R Masser, Laura Otalora, David R Stanford, Arlan Richardson, Willard M Freeman
Brain aging is marked by cognitive decline and susceptibility to neurodegeneration. Calorie restriction (CR) increases neurogenesis, improves memory function, and protects from age-associated neurological disorders. Epigenetic mechanisms, including DNA methylation, are vital to normal central nervous system cellular and memory functions and are dysregulated with aging. The beneficial effects of CR have been proposed to work through epigenetic processes, but this is largely unexplored. We therefore tested whether life long CR prevents age-related hippocampal DNA methylation changes...
March 16, 2018: Neurobiology of Aging
Emil List Larsen, Lucia Padella, Helle Kirstine Mørup Bergholdt, Trine Henriksen, Lucia Santoro, Orazio Gabrielli, Henrik Enghusen Poulsen, Gian Paolo Littarru, Patrick Orlando, Luca Tiano
Elevated levels of oxidative nucleic acid modifications have been proposed to be associated with some of the clinical characteristics of Down syndrome. Oral intake of coenzyme Q10 improves oxidative status and shows a tendency toward protective effect on DNA oxidation in certain age groups of children with Down syndrome. Here, we demonstrate that long-term (i.e., 4 years) treatment with coenzyme Q10 (ubiquinone) at the dosage of 4 mg/kg/d does not affect whole body DNA and RNA oxidation.
March 15, 2018: Neurobiology of Aging
Shiqing Zhang, Ruili Feng, Yanhui Li, Linhua Gan, Fangfang Zhou, Shiquan Meng, Qian Li, Tieqiao Wen
Parkinson's disease (PD) is a common neurodegenerative disease associated with the progressive loss of dopaminergic neurons in the substantia nigra. Proteinaceous depositions of alpha-synuclein (α-syn) and its mutations, A30P and A53T, are one important characteristic of PD. However, little is known about their aggregation and degradation mechanisms. Dendritic cell factor 1 (DCF1) is a membrane protein that plays important roles in nerve development in mouse. In this study, we aimed to show that DCF1 overexpression in a PD Drosophila model significantly ameliorates impaired locomotor behavior in third instar larvae and normalizes neuromuscular junction growth...
March 13, 2018: Neurobiology of Aging
Binbin Wang, Suying Bao, Zhigang Zhang, Xueya Zhou, Jing Wang, Yanhui Fan, Yan Zhang, Yan Li, Luhua Chen, Yizhen Jia, Jiang Li, Miaoxin Li, Wenhua Zheng, Nan Mu, Liqiu Wang, Zhe Yu, Dana S M Wong, Yalun Zhang, Joseph Kwan, Henry Ka-Fung Mak, Amirthagowri Ambalavanan, Sirui Zhou, Wangwei Cai, Jin Zheng, Shishu Huang, Guy A Rouleau, Wanling Yang, Ekaterina Rogaeva, Xu Ma, Peter St George-Hyslop, Leung Wing Chu, You-Qiang Song
Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. To identify rare genetic factors other than apolipoprotein E ɛ4 allele (ApoE ɛ4) contributing to the pathogenesis of late-onset AD (LOAD), we conducted a whole-exome analysis of 246 ApoE ɛ4-negative LOAD cases and 172 matched controls in Hong Kong Chinese population. LOAD patients showed a significantly higher burden of rare loss-of-function variants in genes related to immune function than healthy controls. Among the genes involved in immune function, we identified a rare stop-gain variant (p...
March 10, 2018: Neurobiology of Aging
Eline Wauters, Sara Van Mossevelde, Kristel Sleegers, Julie van der Zee, Sebastiaan Engelborghs, Anne Sieben, Rik Vandenberghe, Stéphanie Philtjens, Marleen Van den Broeck, Karin Peeters, Ivy Cuijt, Wouter De Coster, Tim Van Langenhove, Patrick Santens, Adrian Ivanoiu, Patrick Cras, Jan L De Bleecker, Jan Versijpt, Roeland Crols, Nina De Klippel, Jean-Jacques Martin, Peter P De Deyn, Marc Cruts, Christine Van Broeckhoven
We previously reported a granulin (GRN) null mutation, originating from a common founder, in multiple Belgian families with frontotemporal dementia. Here, we used data of a 10-year follow-up study to describe in detail the clinical heterogeneity observed in this extended founder pedigree. We identified 85 patients and 40 unaffected mutation carriers, belonging to 29 branches of the founder pedigree. Most patients (74.4%) were diagnosed with frontotemporal dementia, while others had a clinical diagnosis of unspecified dementia, Alzheimer's dementia or Parkinson's disease...
March 10, 2018: Neurobiology of Aging
Thomas H McCoy, Kamber Hart, Amelia Pellegrini, Roy H Perlis
We aimed to identify common genetic variations associated with delirium through genome-wide association testing in a hospital biobank. We applied a published electronic health record-based definition of delirium to identify cases of delirium, and control individuals with no history of delirium, from a biobank spanning 2 Boston academic medical centers. Among 6035 individuals of northern European ancestry, including 421 with a history of delirium, we used logistic regression to examine genome-wide association...
March 10, 2018: Neurobiology of Aging
Mario Díaz, Noemí Fabelo, Isidre Ferrer, Raquel Marín
Lipid rafts are highly dynamic membrane domains featured by distinctive biochemical composition and physicochemical properties compared with the surrounding plasma membrane. These microstructures are associated not only with cellular signaling and communication in normal nerve cells but also with pathological processing of amyloid precursor protein in Alzheimer's disease. Using lipid rafts isolated from human frontal cortex in nondemented subjects aging 24 to 85 years, we demonstrate here that lipid structure of lipid rafts undergo significant alterations of specific lipid classes and phospholipid-bound fatty acids as brain cortex correlating with aging...
March 10, 2018: Neurobiology of Aging
Ming Zou, Rui Li, Jian-Yong Wang, Ke Wang, Ya-Nan Wang, Yang Li, Fei-Xue Ji, Sheng-Nan Sun, Shi-Shi Huang, Hui-Hui Fan, Chen-Ping Huang, Xiong Zhang, Jian-Hong Zhu
A recent large-scale European-originated genome-wide association data meta-analysis followed by a replication study identified 6 new risk loci for Parkinson's disease (PD), which include rs10797576/SIPA1L2, rs117896735/INPP5F, rs329648/MIR4697, rs11158026/GCH1, rs2414739/VPS13C, and rs8118008/DDRGK1. However, whether these new loci are associated with PD in Asian populations remain elusive. The INPP5F is nonpolymorphic in Asians. The present study aimed to understand the effects of the other 5 new loci in a Han Chinese population comprising 579 sporadic PD patients and 642 controls...
March 10, 2018: Neurobiology of Aging
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