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Neurobiology of Aging

Adriana L Ruiz-Rizzo, Christian Sorg, Natan Napiórkowski, Julia Neitzel, Aurore Menegaux, Hermann J Müller, Signe Vangkilde, Kathrin Finke
The neural factors that account for the visual processing speed reduction in aging are incompletely understood. Based on previous reports of age-related decreases in the intrinsic functional connectivity (iFC) within the cingulo-opercular network and its relevance for processing speed, we hypothesized that these decreases are associated with age-related reductions in visual processing speed. We used a whole-report task and modeling based on Bundesen's "theory of visual attention" to parameterize visual processing speed in 91 healthy participants aged from 20 to 77 years...
September 21, 2018: Neurobiology of Aging
Cinzia Costa, Michele Romoli, Claudio Liguori, Lucia Farotti, Paolo Eusebi, Chiara Bedetti, Sabrina Siliquini, Elena Nardi Cesarini, Andrea Romigi, Nicola B Mercuri, Lucilla Parnetti, Paolo Calabresi
Although amyloid pathology plays a role in epilepsy, little is known about the relationship between beta amyloid and progression to Alzheimer's disease (AD) among patients with late-onset epilepsy of unknown origin (LOEU). This multicenter, observational, prospective study enrolled 40 consecutive nondemented adults diagnosed with LOEU, together with 43 age- and sex-matched healthy controls. All patients completed neuropsychological tests, core CSF AD biomarkers assessment (Aβ1-42 , total tau, and phosphorylated tau), and follow-up for a mean of 3 years to verify cognitive decline...
September 18, 2018: Neurobiology of Aging
Linyu Zhang, Hao Dong, Youwen Si, Nan Wu, Hao Cao, Bing Mei, Bo Meng
MicroRNAs, small noncoding RNAs, not only regulate gene expression at the post-transcriptional level in a variety of physiological processes but also accompany the initiation and progression of a vast number of diseases, including dementia. While miR-125b has been shown to be aberrantly expressed in some dementia patients, its role in the pathological process remains ambiguous. Presenilin-1/2 conditional double knockout mice exhibit a range of symptoms, including impaired cognition and memory, increased tau phosphorylation, neuroinflammation, and apoptosis, and are therefore regarded as a useful dementia model...
September 18, 2018: Neurobiology of Aging
Uladzislau Rudakou, Bouchra Ouled Amar Bencheikh, Jennifer A Ruskey, Lynne Krohn, Sandra B Laurent, Dan Spiegelman, Christopher Liong, Stanley Fahn, Cheryl Waters, Oury Monchi, Edward A Fon, Yves Dauvilliers, Roy N Alcalay, Nicolas Dupré, Ziv Gan-Or
GCH1 encodes the enzyme guanosine triphospahte (GTP) cyclohydrolase 1, essential for dopamine synthesis in nigrostriatal cells, and rare mutations in GCH1 may lead to Dopa-responsive dystonia (DRD). While GCH1 is implicated in genomewide association studies in Parkinson's disease (PD), only a few studies examined the role of rare GCH1 variants in PD, with conflicting results. In the present study, GCH1 and its 5' and 3' untranslated regions were sequenced in 1113 patients with PD and 1111 controls. To examine the association of rare GCH1 variants with PD, burden analysis was performed...
September 15, 2018: Neurobiology of Aging
Sarah L Gardiner, Aster V E Harder, Yvonne J M Campman, Stella Trompet, Jacobijn Gussekloo, Martine J van Belzen, Merel W Boogaard, Raymund A C Roos, Iris E Jansen, Yolande A L Pijnenburg, Philip Scheltens, Wiesje M van der Flier, N Ahmad Aziz
Genomewide association studies (GWASs) have contributed greatly to unraveling the genetic basis of Alzheimer's disease (AD). However, a large amount of "missing heritability" remains. In this exploratory study, we investigated the effect of cytosine-adenine-guanine (CAG) repeats in polyglutamine disease-associated genes (PDAGs) on the risk of AD and its expression. In a cohort of 959 patients diagnosed with AD (Amsterdam Dementia cohort) and 4106 cognitively healthy participants (Leiden 85-plus Study and the Prospective Study of Pravastatin in the Elderly at Risk), we determined the CAG repeat sequences in ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, HTT, ATN1, and AR...
September 15, 2018: Neurobiology of Aging
Aravindakshan Parthasarathy, Björn Herrmann, Edward L Bartlett
Hearing impairment in older people is thought to arise from impaired temporal processing in auditory circuits. We used a systems-level (scalp recordings) and a microcircuit-level (extracellular recordings) approach to investigate how aging affects the sensitivity to temporal envelopes of speech-like sounds in rats. Scalp-recorded potentials suggest an age-related increase in sensitivity to temporal regularity along the ascending auditory pathway. The underlying cellular changes in the midbrain were examined using extracellular recordings from inferior colliculus neurons...
September 12, 2018: Neurobiology of Aging
Ville Rantalainen, Jari Lahti, Eero Kajantie, Pentti Tienari, Johan G Eriksson, Katri Raikkonen
We tested if the ε4 major isoform of the APOE gene and rs405509 and rs440446 promoter and intron-1 polymorphisms predicted risk of any dementia or Alzheimer's disease with diagnoses derived from the Hospital Discharge and Causes of Death Registers in 1453 participants of the Helsinki Birth Cohort Study. We used Cox proportional hazard models adjusted for sex, year of birth, maximum lifetime occupational status and education, and diagnoses of stroke, coronary heart disease, mood disorders, and depressive symptoms...
September 12, 2018: Neurobiology of Aging
Sun-Ho Han, Jong-Chan Park, Min Soo Byun, Dahyun Yi, Jun Ho Lee, Dong Young Lee, Inhee Mook-Jung
Cerebral β-amyloid (cAβ) deposition and cholinergic dysfunction have been considered as major pathological and functional hallmarks of Alzheimer's disease (AD). Acetylcholinesterase (AChE) is one of the major cholinergic enzymes, and there is no report to show the relationship between cAβ accumulation and peripheral AChE alteration in early stage of AD pathogenesis. Recent studies demonstrate that cAβ starts to deposit 15-20 years ahead of symptomatic appearance and this preclinical AD is important for early diagnosis of disease...
September 8, 2018: Neurobiology of Aging
Atsunobu Suzuki, Mika Ueno, Kenta Ishikawa, Akihiro Kobayashi, Matia Okubo, Toshiharu Nakai
Behavioral studies suggest that older adults may be less adept than younger adults at remembering information contradicting their first impressions about others' trustworthiness. To identify the neural bases associated with such age-related differences, we measured the brain activity of older and younger participants using functional magnetic resonance imaging while they processed feedback on whether their initial trustworthiness impressions of stimulus persons, whose true trustworthiness had been predetermined, were right or wrong...
September 8, 2018: Neurobiology of Aging
Tao Zhang, Xin Jiang, Min Xu, Haifang Wang, Xiao Sang, Meiling Qin, Puhua Bao, Ruiqi Wang, Chenchen Zhang, Huiping Lu, Yuzhuo Li, Jin Ren, Hung-Chun Chang, Jun Yan, Qiang Sun, Jin Xu
Mutations in fused in sarcoma (Fus) cause familial amyotrophic lateral sclerosis (ALS) and occasionally frontotemporal dementia. Here we report the establishment and characterization of a novel knockin (KI) rat model expressing a Fus point mutation (R521C) via CRISPR/Cas9. The mutant animals developed adult-onset learning and memory behavioral deficits, with reduced spine density in hippocampal neurons. Remarkably, sleep-wake cycle and circadian abnormalities preceded the onset of cognitive deficit. RNA-seq study further demonstrated altered expression of some key sleep and circadian regulators, such as orexin/hypocretin receptor type 2 and casein kinase 1 epsilon, in the mutant rats...
September 5, 2018: Neurobiology of Aging
Vanessa Cattaud, Charlotte Bezzina, Christophe C Rey, Camille Lejards, Lionel Dahan, Laure Verret
Recent findings show that parvalbumin (PV) interneuron function is impaired in Alzheimer's disease (AD), and that this impairment in PV function can be linked to network dysfunction and memory deficits. PV cells are often associated with a specific extracellular matrix, the perineuronal net (PNN). PNNs are believed to protect PV cell integrity, and whether the amyloidopathy affects PNNs remains unclear. Here, we evaluated the number of PV cells with and without PNNs in the hippocampus of the Tg2576 mouse model of AD at different stages of the disease...
September 5, 2018: Neurobiology of Aging
Stephanie A Schultz, Brian A Gordon, Shruti Mishra, Yi Su, Richard J Perrin, Nigel J Cairns, John C Morris, Beau M Ances, Tammie L S Benzinger
The objective of this study was to examine the distribution and severity of tau-PET binding in cognitively normal adults with preclinical Alzheimer's disease as determined by positive beta-amyloid PET. 18 F-AV-1451 tau-PET data from 109 cognitively normal older adults were processed with 34 cortical and 9 subcortical FreeSurfer regions and averaged across both hemispheres. Individuals were classified as being beta-amyloid positive (N = 25, A+) or negative (N = 84, A-) based on a 18 F-AV-45 beta-amyloid-PET standardized uptake value ratio of 1...
September 1, 2018: Neurobiology of Aging
Claudio Babiloni, Claudio Del Percio, Roberta Lizio, Giuseppe Noce, Susanna Lopez, Andrea Soricelli, Raffaele Ferri, Maria Teresa Pascarelli, Valentina Catania, Flavio Nobili, Dario Arnaldi, Francesco Famà, Francesco Orzi, Carla Buttinelli, Franco Giubilei, Laura Bonanni, Raffaella Franciotti, Marco Onofrj, Paola Stirpe, Peter Fuhr, Ute Gschwandtner, Gerhard Ransmayr, Lucia Fraioli, Lucilla Parnetti, Lucia Farotti, Michela Pievani, 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, Giovanni B Frisoni, Maria Francesca De Pandis
We hypothesized that dopamine neuromodulation might affect cortical excitability in Parkinson's disease (PD) patients set in quiet wakefulness, as revealed by resting state eyes-closed electroencephalographic (rsEEG) rhythms at alpha frequencies (8-12 Hz). Clinical and rsEEG rhythms in PD with dementia (N = 35), PD with mild cognitive impairment (N = 50), PD with normal cognition (N = 35), and normal (N = 50) older adults were available from an international archive. Cortical rsEEG sources were estimated by exact low-resolution brain electromagnetic tomography...
August 30, 2018: Neurobiology of Aging
Rebecca Deering Brose, Elin Lehrmann, Yongqing Zhang, Roger H Reeves, Kirby D Smith, Mark P Mattson
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by accumulation of amyloid β-peptide (Aβ) plaques in the brain and decreased cognitive function leading to dementia. We tested if hydroxyurea (HU), a ribonucleotide reductase inhibitor known to activate adaptive cellular stress responses and ameliorate abnormalities associated with several genetic disorders, could protect rat hippocampal neurons against oxidative-, excitatory-, mitochondrial-, and Aβ-induced stress and if HU treatment could improve learning and memory in the APP/PS1 mouse model of AD...
August 29, 2018: Neurobiology of Aging
Ryan J Tomm, Maric T Tse, Daniel J Tobiansky, Helen R Schweitzer, Kiran K Soma, Stan B Floresco
Aging is associated with changes in executive functioning and the mesocorticolimbic dopamine system. However, the effects of aging on different forms of behavioral flexibility are not fully characterized. In young (∼5 months) and aged (∼22 months) male Fischer 344 × brown Norway rats, we assessed spatial working memory and different forms of behavioral flexibility using operant tasks: strategy set-shifting (study 1) or probabilistic reversal learning (study 2). We also assessed dopaminergic markers using immunohistochemistry...
August 28, 2018: Neurobiology of Aging
Wendy E Heywood, Jenny Hallqvist, Amanda J Heslegrave, Henrik Zetterberg, Chiara Fenoglio, Elio Scarpini, Jonathan D Rohrer, Daniela Galimberti, Kevin Mills
There is an unmet need for markers that can stratify different forms and subtypes of dementia. Because of similarities in clinical presentation, it can be difficult to distinguish between Alzheimer's disease (AD) and frontotemporal dementia (FTD). Using a multiplex targeted proteomic LC-MS/MS platform, we aimed to identify cerebrospinal fluid proteins differentially expressed between patients with AD and FTD. Furthermore analysis of 2 confirmed FTD genetic subtypes carrying progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72) mutations was performed to give an insight into the differing pathologies of these forms of FTD...
August 25, 2018: Neurobiology of Aging
Tsz Hang Wong, Sven J van der Lee, Jeroen G J van Rooij, Lieke H H Meeter, Petra Frick, Shamiram Melhem, Harro Seelaar, M Arfan Ikram, Annemieke J Rozemuller, Henne Holstege, Marc Hulsman, Andre Uitterlinden, Manuela Neumann, Jeroen J M Hoozemans, Cornelia M van Duijn, Rosa Rademakers, John C van Swieten
Next-generation sequencing has contributed to our understanding of the genetics of Alzheimer's disease (AD) and has explained a substantial part of the missing heritability of familial AD. We sequenced 19 exomes from 8 Dutch families with a high AD burden and identified EIF2AK3, encoding for protein kinase RNA-like endoplasmic reticulum kinase (PERK), as a candidate gene. Gene-based burden analysis in a Dutch AD exome cohort containing 547 cases and 1070 controls showed a significant association of EIF2AK3 with AD (OR 1...
August 24, 2018: Neurobiology of Aging
Xiang Chen, Yousheng Xiao, Wenyuan Guo, Miaomiao Zhou, Shuxuan Huang, Mingshu Mo, Zhe Li, Guihua Li, Hanqun Liu, Guoyou Peng, Zhuohua Wu, Yijuan Wu, Chaohao Yang, Zhong Pei, Chaojun Chen, Pingyi Xu
Genetic factors play significant roles in the causes of Parkinson's disease (PD). Recently, a meta-analysis of genome-wide association study (GWAS) has identified 17 loci associated with PD. The objective of our study was to investigate the association of 17 single-nucleotide polymorphisms with the risk of PD in Chinese population. We performed a case-control association study, and 1189 subjects comprising 652 PD patients and 537 controls were genotyped by using a Mass ARRAY System or a TaqMan assay. We found that rs601999 (OR (95% CI) = 3...
August 24, 2018: Neurobiology of Aging
Agnès Lacreuse, Lisa Parr, Lakshmi Chennareddi, James G Herndon
Data on cognitive aging in chimpanzees are extremely sparse, yet can provide an invaluable phylogenetic perspective, especially because Alzheimer disease (AD)-like neuropathology has recently been described in the oldest chimpanzee brains. This finding underscores the importance of data on cognitive aging in this fellow hominin, our closest biological relative. We tested 30 female chimpanzees, 12-56 years old, on a computerized analog of the Wisconsin Card Sort test. This test assesses cognitive flexibility, which is severely impaired in normal aging and AD...
August 24, 2018: Neurobiology of Aging
Antonio Canosa, Giovanni De Marco, Annarosa Lomartire, Maria Teresa Rinaudo, Ferdinando Di Cunto, Emilia Turco, Marco Barberis, Maura Brunetti, Federico Casale, Cristina Moglia, Andrea Calvo, Stefan L Marklund, Peter M Andersen, Gabriele Mora, Adriano Chiò
We report an apparently sporadic amyotrophic lateral sclerosis patient carrying a heterozygous novel frameshift SOD1 mutation (p.Ser108LeufsTer15), predicted to cause a premature protein truncation. RT-PCR analysis of SOD1 mRNA and SDS-PAGE/Western blot analysis of PBMC demonstrated that mRNA from the mutant allele is expressed at levels similar to those of the wild-type allele, but the truncated protein is undetectable also in the insoluble fraction and after proteasome inhibition. Accordingly, the dismutation activity in erythrocytes is halved...
August 24, 2018: Neurobiology of Aging
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