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Neurobiology of Aging

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https://www.readbyqxmd.com/read/28646686/eeg-spectral-analysis-as-a-putative-early-prognostic-biomarker-in-nondemented-amyloid-positive-subjects
#1
Alida A Gouw, Astrid M Alsema, Betty M Tijms, Andreas Borta, Philip Scheltens, Cornelis J Stam, Wiesje M van der Flier
We studied whether electroencephalography (EEG)-derived measures of brain oscillatory activity are related to clinical progression in nondemented, amyloid positive subjects. We included 205 nondemented amyloid positive subjects (63 subjective cognitive decline [SCD]; 142 mild cognitive impairment [MCI]) with a baseline resting-state EEG data and ≥1-year follow-up. Peak frequency and relative power of 4 frequency bands were calculated. Relationships between normalized EEG measures and time to clinical progression (conversion from SCD to MCI/dementia or from MCI to dementia) were analyzed using Cox proportional hazard models...
June 1, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28646687/cortical-amyloid-accumulation-is-associated-with-alterations-of-structural-integrity-in-older-people-with-subjective-memory-complaints
#2
Stefan J Teipel, Enrica Cavedo, Sarah Weschke, Michel J Grothe, Katrine Rojkova, Gaëlle Fontaine, Luce Dauphinot, Gabriel Gonzalez-Escamilla, Marie-Claude Potier, Hugo Bertin, Marie-Odile Habert, Bruno Dubois, Harald Hampel
We determined the effect of cortical amyloid load using (18)F-florbetapir PET on cognitive performance and gray matter structural integrity derived from MRI in 318 cognitively normally performing older people with subjective memory impairment from the INSIGHT-preAD cohort using multivariate partial least squares regression. Amyloid uptake was associated with reduced gray matter structural integrity in hippocampus, entorhinal and cingulate cortex, middle temporal gyrus, prefrontal cortex, and lentiform nucleus (p < 0...
May 31, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28628896/cholinergic-neuron-gene-expression-differences-captured-by-translational-profiling-in-a-mouse-model-of-alzheimer-s-disease
#3
Paul M McKeever, TaeHyung Kim, Andrew R Hesketh, Laura MacNair, Denise Miletic, Giorgio Favrin, Stephen G Oliver, Zhaolei Zhang, Peter St George-Hyslop, Janice Robertson
Cholinergic neurotransmission is impaired in Alzheimer's disease (AD), and loss of basal forebrain cholinergic neurons is a key component of disease pathogenicity and symptomatology. To explore the molecular basis of this cholinergic dysfunction, we paired translating ribosome affinity purification (TRAP) with RNA sequencing (TRAP-Seq) to identify the actively translating mRNAs in anterior forebrain cholinergic neurons in the TgCRND8 mouse model of AD. Bioinformatic analyses revealed the downregulation of 67 of 71 known cholinergic-related transcripts, consistent with cholinergic neuron dysfunction in TgCRND8 mice, as well as transcripts related to oxidative phosphorylation, neurotrophins, and ribosomal processing...
May 25, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28624616/age-related-plasticity-of-the-axon-initial-segment-of-cortical-pyramidal-cells-in-marmoset-monkeys
#4
Nafiseh Atapour, Marcello G P Rosa
Structural plasticity of the axon initial segment (AIS), the site of action potential initiation, is observed as part of the normal early development of the cortex, as well as in association with injury and disease. Here, we show that structural AIS plasticity also occurs with normal aging in adult marmosets. Immunohistochemical techniques were used to reveal the extent of the AIS of layer 2/3A pyramidal cells in 8 neocortical areas. We found that the AIS length varied significantly between areas in young adult (2-3 years old) marmosets, with neurons in frontal area 14C having the longest AIS, and those in the primary visual cortex the shortest...
May 22, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28605641/spectral-and-temporal-auditory-processing-in-the-superior-colliculus-of-aged-rats
#5
Margarida Costa, Franco Lepore, Jean-Paul Guillemot
Presbyacusis reflects dysfunctions present along the central auditory pathway. Given that the topographic representation of the auditory directional spatial map is deteriorated in the superior colliculus of aged animals, therefore, are spectral and temporal auditory processes altered with aging in the rat's superior colliculus? Extracellular single-unit recordings were conducted in the superior colliculus of anesthetized Sprague-Dawley adult (10 months) and aged (22 months) rats. In the spectral domain, level thresholds in aged rats were significantly increased when superior colliculus auditory neurons were stimulated with pure tones or Gaussian noise bursts...
May 22, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28609678/glucocorticoid-mediated-activation-of-gsk3%C3%AE-promotes-tau-phosphorylation-and-impairs-memory-in-type-2-diabetes
#6
Aditi Dey, Shuai Hao, Marlena Wosiski-Kuhn, Alexis M Stranahan
Type 2 diabetes is increasingly recognized as a risk factor for Alzheimer's disease, but the underlying mechanisms remain poorly understood. Hyperphosphorylation of the microtubule-associated protein tau has been reported in rodent models of diabetes, including db/db mice, which exhibit insulin resistance and chronically elevated glucocorticoids due to leptin receptor insufficiency. In this report, we investigated endocrine mechanisms for hippocampal tau phosphorylation in db/db and wild-type mice. By separately manipulating peripheral and intrahippocampal corticosterone levels, we determined that hippocampal corticosteroid exposure promotes tau phosphorylation and activates glycogen synthase kinase 3β (GSK3β)...
May 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28602509/neurochip-an-updated-version-of-the-neurox-genotyping-platform-to-rapidly-screen-for-variants-associated-with-neurological-diseases
#7
Cornelis Blauwendraat, Faraz Faghri, Lasse Pihlstrom, Joshua T Geiger, Alexis Elbaz, Suzanne Lesage, Jean-Christophe Corvol, Patrick May, Aude Nicolas, Yevgeniya Abramzon, Natalie A Murphy, J Raphael Gibbs, Mina Ryten, Raffaele Ferrari, Jose Bras, Rita Guerreiro, Julie Williams, Rebecca Sims, Steven Lubbe, Dena G Hernandez, Kin Y Mok, Laurie Robak, Roy H Campbell, Ekaterina Rogaeva, Bryan J Traynor, Ruth Chia, Sun Ju Chung, John A Hardy, Alexis Brice, Nicholas W Wood, Henry Houlden, Joshua M Shulman, Huw R Morris, Thomas Gasser, Rejko Krüger, Peter Heutink, Manu Sharma, Javier Simón-Sánchez, Mike A Nalls, Andrew B Singleton, Sonja W Scholz
Genetics has proven to be a powerful approach in neurodegenerative diseases research, resulting in the identification of numerous causal and risk variants. Previously, we introduced the NeuroX Illumina genotyping array, a fast and efficient genotyping platform designed for the investigation of genetic variation in neurodegenerative diseases. Here, we present its updated version, named NeuroChip. The NeuroChip is a low-cost, custom-designed array containing a tagging variant backbone of about 306,670 variants complemented with a manually curated custom content comprised of 179,467 variants implicated in diverse neurological diseases, including Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy...
May 17, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28641921/genome-wide-association-and-interaction-studies-of-csf-t-tau-a%C3%AE-42-ratio-in-adni-cohort
#8
Jin Li, Qiushi Zhang, Feng Chen, Xianglian Meng, Wenjie Liu, Dandan Chen, Jingwen Yan, Sungeun Kim, Lei Wang, Weixing Feng, Andrew J Saykin, Hong Liang, Li Shen
The pathogenic relevance in Alzheimer's disease (AD) presents a decrease of cerebrospinal fluid amyloid-ß42 (Aß42) burden and an increase in cerebrospinal fluid total tau (T-tau) levels. In this work, we performed genome-wide association study (GWAS) and genome-wide interaction study of T-tau/Aß42 ratio as an AD imaging quantitative trait on 843 subjects and 563,980 single-nucleotide polymorphisms (SNPs) in ADNI cohort. We aim to identify not only SNPs with significant main effects but also SNPs with interaction effects to help explain "missing heritability"...
May 15, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28605642/applicability-of-11-c-pib-micro-pet-imaging-for-in%C3%A2-vivo-follow-up-of-anti-amyloid-treatment-effects-in-app23-mouse-model
#9
Anniina Snellman, Johanna Rokka, Francisco R López-Picón, Semi Helin, Francesca Re, Eliisa Löyttyniemi, Rea Pihlaja, Gianluigi Forloni, Mario Salmona, Massimo Masserini, Olof Solin, Juha O Rinne, Merja Haaparanta-Solin
In this study, we evaluated the anti-amyloid effect of functionalized nanoliposomes (mApoE-PA-LIP) in a mouse model of Alzheimer's disease with use of positron emission tomography and β-amyloid (Aβ)-targeted tracer [(11)C]Pittsburgh compound B ([(11)C]PIB). APP23 mice were injected with mApoE-PA-LIP or saline (3 times per week for 3 weeks) and [(11)C]PIB imaging was performed at baseline, after the treatment and after 3 months follow-up period, accompanied by Aβ immunohistochemistry and ELISA. After the treatment, [(11)C]PIB binding ratios between mApoE-PA-LIP and saline groups were equivalent in all analyzed brain regions; however, in the saline group, binding ratios increased from the baseline, whereas no increase was detected in the mApoE-PA-LIP group...
May 15, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28599217/reduced-dopamine-receptors-and-transporters-but-not-synthesis-capacity-in-normal-aging-adults-a-meta-analysis
#10
Teresa M Karrer, Anika K Josef, Rui Mata, Evan D Morris, Gregory R Samanez-Larkin
Many theories of cognitive aging are based on evidence that dopamine (DA) declines with age. Here, we performed a systematic meta-analysis of cross-sectional positron emission tomography and single-photon emission-computed tomography studies on the average effects of age on distinct DA targets (receptors, transporters, or relevant enzymes) in healthy adults (N = 95 studies including 2611 participants). Results revealed significant moderate to large, negative effects of age on DA transporters and receptors...
May 12, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28641136/age-exacerbates-abnormal-protein-expression-in-a-mouse-model-of-down-syndrome
#11
Md Mahiuddin Ahmed, Aaron Block, Suhong Tong, Muriel T Davisson, Katheleen J Gardiner
The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at ∼6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer's disease...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28599986/a-call-for-new-approaches-to-alzheimer-s-disease-research
#12
Paul D Coleman, Diego Mastroeni
No abstract text is available yet for this article.
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28595105/docosahexaenoic-acid-prevents-cognitive-deficits-in-human-apolipoprotein-e-epsilon-4-targeted-replacement-mice
#13
Raphaël Chouinard-Watkins, Milène Vandal, Pauline Léveillé, Anthony Pinçon, Frédéric Calon, Mélanie Plourde
At a population level, dietary consumption of fish rich in docosahexaenoic acid (DHA) is associated with prevention of cognitive decline but this association is not clear in carriers of the apolipoprotein E epsilon 4 allele (E4). Plasma and liver DHA concentrations show significant alterations in E4 carriers, in part corrected by DHA supplementation. However, whether DHA sufficiency in E4 carriers has consequences on cognition is unknown. Mice expressing human E4 or apolipoprotein E epsilon 3 allele (E3) were fed either a control diet or a diet containing DHA for 8 months and cognitive performance was tested using the object recognition test and the Barnes maze test...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28578155/prefrontal-parietal-effective-connectivity-during-working-memory-in-older-adults
#14
Stephan Heinzel, Robert C Lorenz, Quynh-Lam Duong, Michael A Rapp, Lorenz Deserno
Theoretical models and preceding studies have described age-related alterations in neuronal activation of frontoparietal regions in a working memory (WM) load-dependent manner. However, to date, underlying neuronal mechanisms of these WM load-dependent activation changes in aging remain poorly understood. The aim of this study was to investigate these mechanisms in terms of effective connectivity by application of dynamic causal modeling with Bayesian Model Selection. Eighteen healthy younger (age: 20-32 years) and 32 older (60-75 years) participants performed an n-back task with 3 WM load levels during functional magnetic resonance imaging (fMRI)...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28577411/tau-pathology-and-cognitive-reserve-in-alzheimer-s-disease
#15
Merle Christine Hoenig, Gérard Nisal Bischof, Jochen Hammes, Jennifer Faber, Klaus Fliessbach, Thilo van Eimeren, Alexander Drzezga
Cognitive reserve (CR) is defined as the ability to maintain functionality despite accumulating pathology. Education has been used as a proxy for CR. For example, by using positron emission tomography imaging, higher educated Alzheimer's disease (AD) patients presented increased amyloid β pathology than lower educated patients despite equal symptomatology. Whether similar associations exist for in vivo tau pathology remains elusive. We utilized [(18)F]AV-1451 positron emission tomography imaging to examine whether high-educated AD patients (n = 12) present more severe tau pathology compared with low-educated patients (n = 12) despite equal clinical severity in regions of interest corresponding to the pathologic disease stages defined by Braak & Braak...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28571652/functional-neuroanatomy-of-speech-signal-decoding-in-primary-progressive-aphasias
#16
Chris J D Hardy, Jennifer L Agustus, Charles R Marshall, Camilla N Clark, Lucy L Russell, Emilie V Brotherhood, Rebecca L Bond, Cassidy M Fiford, Sasha Ondobaka, David L Thomas, Sebastian J Crutch, Jonathan D Rohrer, Jason D Warren
The pathophysiology of primary progressive aphasias remains poorly understood. Here, we addressed this issue using activation fMRI in a cohort of 27 patients with primary progressive aphasia (nonfluent, semantic, and logopenic variants) versus 15 healthy controls. Participants listened passively to sequences of spoken syllables in which we manipulated 3-key auditory speech signal characteristics: temporal regularity, phonemic spectral structure, and pitch sequence entropy. Relative to healthy controls, nonfluent variant patients showed reduced activation of medial Heschl's gyrus in response to any auditory stimulation and reduced activation of anterior cingulate to temporal irregularity...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28559106/disregarding-hearing-loss-leads-to-overestimation-of-age-related-cognitive-decline
#17
Maria J S Guerreiro, Pascal W M Van Gerven
Aging is associated with cognitive and sensory decline. While several studies have indicated greater cognitive decline among older adults with hearing loss, the extent to which age-related differences in cognitive processing may have been overestimated due to group differences in sensory processing has remained unclear. We addressed this question by comparing younger adults, older adults with good hearing, and older adults with poor hearing in several cognitive domains: working memory, selective attention, processing speed, inhibitory control, and abstract reasoning...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28578804/human-anterolateral-entorhinal-cortex-volumes-are-associated-with-cognitive-decline-in-aging-prior-to-clinical-diagnosis
#18
Rosanna K Olsen, Lok-Kin Yeung, Alix Noly-Gandon, Maria C D'Angelo, Arber Kacollja, Victoria M Smith, Jennifer D Ryan, Morgan D Barense
We investigated whether older adults without subjective memory complaints, but who present with cognitive decline in the laboratory, demonstrate atrophy in medial temporal lobe (MTL) subregions associated with Alzheimer's disease. Forty community-dwelling older adults were categorized based on Montreal Cognitive Assessment (MoCA) performance. Total gray/white matter, cerebrospinal fluid, and white matter hyperintensity load were quantified from whole-brain T1-weighted and fluid-attenuated inversion recovery magnetic resonance imaging scans, whereas hippocampal subfields and MTL cortical subregion volumes (CA1, dentate gyrus/CA2/3, subiculum, anterolateral and posteromedial entorhinal, perirhinal, and parahippocampal cortices) were quantified using high-resolution T2-weighted scans...
May 8, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28552181/white-matter-integrity-on-dti-and-the-pathologic-staging-of-alzheimer-s-disease
#19
Kejal Kantarci, Melissa E Murray, Christopher G Schwarz, Robert I Reid, Scott A Przybelski, Timothy Lesnick, Samantha M Zuk, Mekala R Raman, Matthew L Senjem, Jeffrey L Gunter, Bradley F Boeve, David S Knopman, Joseph E Parisi, Ronald C Petersen, Clifford R Jack, Dennis W Dickson
Pattern of diffusion tensor MRI (DTI) alterations were investigated in pathologically-staged Alzheimer's disease (AD) patients (n = 46). Patients with antemortem DTI studies and a range of AD pathology at autopsy were included. Patients with a high neurofibrillary tangle (NFT) stage (Braak IV-VI) had significantly elevated mean diffusivity (MD) in the crus of fornix and ventral cingulum tracts, precuneus, and entorhinal white matter on voxel-based analysis after adjusting for age and time from MRI to death (p < 0...
May 4, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28600952/time-course-of-tau-toxicity-and-pharmacologic-prevention-in-a-cell%C3%A2-model-of-tauopathy
#20
Marcus Pickhardt, Jacek Biernat, Sabrina Hübschmann, Frank J A Dennissen, Thomas Timm, Annukka Aho, Eva-Maria Mandelkow, Eckhard Mandelkow
The aggregation of Tau protein is a hallmark of neurodegenerative diseases including Alzheimer's disease. Previously, we generated a cell model of tauopathy based on the 4-repeat domain with the FTDP-17 mutation ΔK280 (Tau(4RDΔK)) which is expressed in a regulatable fashion (tet-on). The deletion variant ΔK280 is highly amyloidogenic and forms fibrous aggregates in neuroblastoma N2a cells staining with the reporter dye Thioflavin S. The aggregation of Tau(4RDΔK) is toxic, contrary to wildtype or anti-aggregant variants of the protein...
May 3, 2017: Neurobiology of Aging
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