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Neurobiology of Aging

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https://www.readbyqxmd.com/read/28780367/differential-effects-of-blood-insulin-and-hba1c-on-cerebral-amyloid-burden-and-neurodegeneration-in-nondiabetic-cognitively-normal-older-adults
#1
Min Soo Byun, Hyun Jung Kim, Dahyun Yi, Hyo Jung Choi, Hyewon Baek, Jun Ho Lee, Young Min Choe, Bo Kyung Sohn, Jun-Young Lee, Younghwa Lee, Hyunwoong Ko, Yu Kyeong Kim, Yun-Sang Lee, Chul-Ho Sohn, Jong Inn Woo, Dong Young Lee
We tested the hypothesis that lower insulin or higher glycated hemoglobin (HbA1c) levels in blood are associated with increased cerebral beta amyloid (Aβ) deposition and neurodegeneration in nondiabetic cognitively normal (CN) older adults. A total of 205 nondiabetic CN older adults underwent comprehensive clinical assessment, [(11)C]Pittsburgh compound B (PiB)-positron emission tomography (PET), [(18)F]fluorodeoxyglucose-PET, magnetic resonance imaging, and blood sampling for fasting insulin and HbA1c measurement...
July 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28800410/incident-risk-and-progression-of-cerebral-microbleeds-in-healthy-adults-a-multi-occasion-longitudinal-study
#2
Ana M Daugherty, Naftali Raz
Decline in cerebrovascular health complicates brain aging, and development of cerebral microbleeds (CMBs) is one of its prominent indicators. In a large sample of healthy adults (N = 251, age 18-78 years at baseline, 70% women), the contributions of chronological age and vascular health indicators to the risk of developing a CMB, as well as the change in CMB size and iron content, were examined in a prospective 8-year longitudinal study using susceptibility weighted imaging. Twenty-six persons (10.4%), most of whom were 40 years of age or older, had at least 1 CMB during the study...
July 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28780366/transthyretin-neuroprotection-in-alzheimer-s-disease-is-dependent-on-proteolysis
#3
Catarina S Silva, Jessica Eira, Carlos A Ribeiro, Ângela Oliveira, Mónica M Sousa, Isabel Cardoso, Márcia A Liz
The deposition of amyloid β peptide (Aβ) in the hippocampus is one of the major hallmarks of Alzheimer's disease, a neurodegenerative disorder characterized by memory loss and cognitive impairment. The modulation of Aβ levels in the brain results from an equilibrium between its production from the amyloid precursor protein and removal by amyloid clearance proteins, which might occur via enzymatic (Aβ-degrading enzymes) or nonenzymatic (binding/transport proteins) reactions. Transthyretin (TTR) is one of the major Aβ-binding proteins acting as a neuroprotector in AD...
July 15, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28789839/contribution-to-alzheimer-s-disease-risk-of-rare-variants-in-trem2-sorl1-and-abca7-in-1779-cases-and-1273-controls
#4
Céline Bellenguez, Camille Charbonnier, Benjamin Grenier-Boley, Olivier Quenez, Kilan Le Guennec, Gaël Nicolas, Ganesh Chauhan, David Wallon, Stéphane Rousseau, Anne Claire Richard, Anne Boland, Guillaume Bourque, Hans Markus Munter, Robert Olaso, Vincent Meyer, Adeline Rollin-Sillaire, Florence Pasquier, Luc Letenneur, Richard Redon, Jean-François Dartigues, Christophe Tzourio, Thierry Frebourg, Mark Lathrop, Jean-François Deleuze, Didier Hannequin, Emmanuelle Genin, Philippe Amouyel, Stéphanie Debette, Jean-Charles Lambert, Dominique Campion
We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer disease (LOAD) cases, 852 early-onset AD (EOAD) cases, and 1273 controls from France. We assessed the evidence for gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein-truncating and missense-predicted damaging variants, we found exome-wide significant association between EOAD risk and rare variants in SORL1, TREM2, and ABCA7. No exome-wide significant signal was obtained in the LOAD sample, and significance of the order of 10(-6) was observed in the whole AD group for TREM2...
July 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28779628/csf-serum-albumin-ratio-in-dementias-a-cross-sectional-study-on-1861-patients
#5
Tobias Skillbäck, Louise Delsing, Jane Synnergren, Niklas Mattsson, Shorena Janelidze, Katarina Nägga, Lena Kilander, Ryan Hicks, Anders Wimo, Bengt Winblad, Oskar Hansson, Kaj Blennow, Maria Eriksdotter, Henrik Zetterberg
A connection between dementias and blood-brain barrier (BBB) dysfunction has been suggested, but previous studies have yielded conflicting results. We examined cerebrospinal fluid (CSF)/serum albumin ratio in a large cohort of patients diagnosed with Alzheimer's disease (AD, early onset [EAD, n = 130], late onset AD [LAD, n = 666]), vascular dementia (VaD, n = 255), mixed AD and VaD (MIX, n = 362), Lewy body dementia (DLB, n = 50), frontotemporal dementia (FTD, n = 56), Parkinson's disease dementia (PDD, n = 23), other dementias (other, n = 48), and dementia not otherwise specified (NOS, n = 271)...
July 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28756942/identifying-incipient-dementia-individuals-using-machine-learning-and-amyloid-imaging
#6
Sulantha Mathotaarachchi, Tharick A Pascoal, Monica Shin, Andrea L Benedet, Min Su Kang, Thomas Beaudry, Vladimir S Fonov, Serge Gauthier, Pedro Rosa-Neto
Identifying individuals destined to develop Alzheimer's dementia within time frames acceptable for clinical trials constitutes an important challenge to design studies to test emerging disease-modifying therapies. Although amyloid-β protein is the core pathologic feature of Alzheimer's disease, biomarkers of neuronal degeneration are the only ones believed to provide satisfactory predictions of clinical progression within short time frames. Here, we propose a machine learning-based probabilistic method designed to assess the progression to dementia within 24 months, based on the regional information from a single amyloid positron emission tomography scan...
July 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28756941/peripheral-lipid-oxidative-stress-markers-are-related-to-vascular-risk-factors-and-subcortical-small-vessel-disease
#7
Walter Swardfager, Di Yu, Gustavo Scola, Hugo Cogo-Moreira, Parco Chan, Yi Zou, Nathan Herrmann, Krista L Lanctôt, Joel Ramirez, Fuqiang Gao, Mario Masellis, Richard H Swartz, Demetrios J Sahlas, Pak Cheung Chan, Carmen Ojeda-Lopez, Angela Milan-Tomas, Jacqueline A Pettersen, Ana C Andreazza, Sandra E Black
Subcortical white matter hyperintensities (WMH), presumed to indicate small vessel ischemic vascular disease, are found commonly in elderly individuals with and without Alzheimer's disease (AD). Oxidative stress may instigate or accelerate the development of vascular disease, and oxidative stress markers are elevated in AD. Here, we assess independent relationships between three serum lipid peroxidation markers (lipid hydroperoxides [LPH], 8-isoprostane, and 4-hydroxynonenal) and the presence of extensive subcortical WMH and/or AD...
July 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28735144/entorhinal-tau-pathology-disrupts-hippocampal-prefrontal-oscillatory-coupling-during-associative-learning
#8
Stephanie E Tanninen, Bardia Nouriziabari, Mark D Morrissey, Rami Bakir, Robert D Dayton, Ronald L Klein, Kaori Takehara-Nishiuchi
A neural signature of asymptomatic preclinical Alzheimer's disease (AD) is disrupted connectivity between brain regions; however, its underlying mechanisms remain unknown. Here, we tested whether a preclinical pathologic feature, tau aggregation in the entorhinal cortex (EC) is sufficient to disrupt the coordination of local field potentials (LFPs) between its efferent regions. P301L-mutant human tau or green fluorescent protein (GFP) was virally overexpressed in the EC of adult rats. LFPs were recorded from the dorsal hippocampus and prelimbic medial prefrontal cortex while the rats underwent trace eyeblink conditioning where they learned to associate 2 stimuli separated by a short time interval...
July 6, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28735143/transcranial-low-level-laser-therapy-improves-brain-mitochondrial-function-and-cognitive-impairment-in-d-galactose-induced-aging-mice
#9
Farzad Salehpour, Nahid Ahmadian, Seyed Hossein Rasta, Mehdi Farhoudi, Pouran Karimi, Saeed Sadigh-Eteghad
Mitochondrial function plays a key role in the aging-related cognitive impairment, and photoneuromodulation of mitochondria by transcranial low-level laser therapy (LLLT) may contribute to its improvement. This study focused on the transcranial LLLT effects on the D-galactose (DG)-induced mitochondrial dysfunction, apoptosis, and cognitive impairment in mice. For this purpose, red and near-infrared (NIR) laser wavelengths (660 and 810 nm) at 2 different fluencies (4 and 8 J/cm(2)) at 10-Hz pulsed wave mode were administrated transcranially 3 d/wk in DG-received (500 mg/kg/subcutaneous) mice model of aging for 6 weeks...
July 6, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28750307/resilient-protein-co-expression-network-in-male-orbitofrontal-cortex-layer-2-3-during-human-aging
#10
Mohan Pabba, Enzo Scifo, Fenika Kapadia, Yuliya S Nikolova, Tianzhou Ma, Naguib Mechawar, George C Tseng, Etienne Sibille
The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging. Currently, layer resolution large-scale proteomic studies describing "normal" age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects. We detected 4193 proteins and identified 127 differentially expressed (DE) proteins (p-value ≤0.05; effect size >20%), including 65 up- and 62 downregulated proteins (e...
July 5, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28732249/evaluating-alzheimer-s-disease-biomarkers-as-mediators-of-age-related-cognitive-decline
#11
Timothy J Hohman, Doug Tommet, Shawn Marks, Joey Contreras, Rich Jones, Dan Mungas
Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes...
July 4, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28734217/emotional-arousal-and-recognition-memory-are-differentially-reflected-in-pupil-diameter-responses-during-emotional-memory-for-negative-events-in-younger-and-older-adults
#12
Dorothea Hämmerer, Alexandra Hopkins, Matthew J Betts, Anne Maaß, Ray J Dolan, Emrah Düzel
A better memory for negative emotional events is often attributed to a conjoint impact of increased arousal and noradrenergic modulation (NA). A decline in NA during aging is well documented but its impact on memory function during aging is unclear. Using pupil diameter (PD) as a proxy for NA, we examined age differences in memory for negative events in younger (18-30 years) and older (62-83 years) adults based on a segregation of early arousal to negative events, and later retrieval-related PD responses...
June 30, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28746897/parkinsonian-features-in-aging-gfap-hmox1-transgenic-mice-overexpressing-human-ho-1-in-the-astroglial-compartment
#13
Wei Song, Marisa Cressatti, Hillel Zukor, Adrienne Liberman, Carmela Galindez, Hyman M Schipper
Epigenetic influences mediating brain iron deposition, oxidative mitochondrial injury, and macroautophagy in Parkinson disease and related conditions remain enigmatic. Here, we show that selective overexpression of the stress protein, heme oxygenase-1 (HO-1) in astrocytes of GFAP.HMOX1 transgenic mice between 8.5 and 19 months of age results in nigrostriatal hypodopaminergia associated with locomotor incoordination and stereotypy; downregulation of tyrosine hydroxylase, DAT, LMX1B, Nurr1, Pitx3 and DJ-1 mRNA and/or protein; overproduction of α-synuclein and ubiquitin; oxidative stress; basal ganglia siderosis; mitochondrial damage/mitophagy; and augmented GABAergic systems (increased GABA, GAD67 and reelin)...
June 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28716534/mutations-in-tyrobp-are-not-a-common-cause-of-dementia-in-a-turkish-cohort
#14
Lee Darwent, Susana Carmona, Ebba Lohmann, Gamze Guven, Celia Kun-Rodrigues, Basar Bilgic, Hasmet Hanagasi, Hakan Gurvit, Nihan Erginel-Unaltuna, Meltem Pak, John Hardy, Andrew Singleton, Jose Brás, Rita Guerreiro
Mutations in TYROBP and TREM2 have been shown to cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. Recently, variants in TREM2 were also associated with frontotemporal dementia and Alzheimer's disease. Given the functional proximity between these 2 genes, we investigated the genetic variation of TYROBP in a Turkish cohort of 103 dementia patients. No mutations or copy number variants predicted to be pathogenic were identified. These results indicate that mutations in TYROBP are not a common cause of dementia in this Turkish cohort...
June 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28764930/association-between-educational-attainment-and-amyloid-deposition-across-the-spectrum-from-normal-cognition-to-dementia-neuroimaging-evidence-for-protection-and-compensation
#15
Eider M Arenaza-Urquijo, Alexandre Bejanin, Julie Gonneaud, Miranka Wirth, Renaud La Joie, Justine Mutlu, Malo Gaubert, Brigitte Landeau, Vincent de la Sayette, Francis Eustache, Gaël Chételat
The brain mechanisms underlying the effect of intellectual enrichment may evolve along the normal aging Alzheimer's disease (AD) cognitive spectrum and may include both protective and compensatory mechanisms. We assessed the association between early intellectual enrichment (education, years) and average cortical florbetapir standardized uptake value ratio as well as performed voxel-wise analyses in a total of 140 participants, including cognitively normal older adults, mild cognitive impairment (MCI), and AD patients...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28755648/cerebral-pet-glucose-hypometabolism-in-subjects-with-mild-cognitive-impairment-and-higher-eeg-high-alpha-low-alpha-frequency-power-ratio
#16
Davide Vito Moretti, Michela Pievani, Lorenzo Pini, Ugo Paolo Guerra, Barbara Paghera, Giovanni Battista Frisoni
In Alzheimer's disease (AD) research, both 2-deoxy-2-((18)F)fluoro-D-glucose (FDG) positron emission tomography (PET) and electroencephalography (EEG) are reliable investigational modalities. The aim of this study was to investigate the associations between EEG High-alpha/Low-alpha (H-alpha/L-alpha) power ratio and cortical glucose metabolism. A total of 23 subjects with mild cognitive impairment (MCI) underwent FDG-PET and EEG examinations. H-alpha/L-alpha power ratio was computed for each subject and 2 groups were obtained based on the increase of the power ratio...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28753475/presenilin-1-mutation-decreases-both-calcium-and-contractile-responses-in-cerebral-arteries
#17
Xavier Toussay, Jean-Luc Morel, Nathalie Biendon, Lolita Rotureau, François-Pierre Legeron, Marie-Charlotte Boutonnet, Yoon H Cho, Nathalie Macrez
Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca(2+)) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca(2+) signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28753474/age-related-changes-in-envelope-following-responses-at-equalized-peripheral-or-central-activation
#18
Jesyin Lai, Alexandra L Sommer, Edward L Bartlett
Previous work has debated about the comparisons of hearing abilities faced with alterations in hearing thresholds and evoked potentials between groups following acoustic trauma- or age-related changes. This study compares envelope-following responses (EFRs) of young and aged rats when sound levels were matched according to (1) wave I amplitudes of auditory brainstem responses (ABRs) elicited by 8-kHz tones or (2) EFR amplitudes evoked by sinusoidally amplitude-modulated (SAM) tones at 100% depth. Matched wave I amplitudes across age corresponded to approximately 20-dB sound level differences...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28728889/cognitive-and-motor-functioning-in-elderly-glucocerebrosidase-mutation-carriers
#19
Eileen E Moran, Cuiling Wang, Mindy Katz, Laurie Ozelius, Alison Schwartz, Jelena Pavlovic, Roberto A Ortega, Richard B Lipton, Molly E Zimmerman, Rachel Saunders-Pullman
Mutations in the glucocerebrosidase (GBA) gene are a strong genetic risk factor for the development of Parkinson's disease and dementia with Lewy Bodies. However the penetrance of GBA mutations is low for these diseases in heterozygous carriers. The aim of this study was to examine the relationship between mutation status and cognitive and motor functioning in a sample of community-dwelling older adults. Using linear mixed effects models, we examined the effect of heterozygous mutation status on 736 community-dwelling older adults (≥70 years) without dementia or Parkinson's disease assessed over an average of 6 years, 28 of whom had a single GBA mutation (primarily N370S)...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28728117/alzheimer-s-disease-markers-in-the-aged-sheep-ovis-aries
#20
Suzanne J Reid, Natasha E Mckean, Kristen Henty, Erik Portelius, Kaj Blennow, Skye R Rudiger, C Simon Bawden, Renee R Handley, Paul J Verma, Richard L M Faull, Henry J Waldvogel, Henrik Zetterberg, Russell G Snell
This study reports the identification and characterization of markers of Alzheimer's disease (AD) in aged sheep (Ovis aries) as a preliminary step toward making a genetically modified large animal model of AD. Importantly, the sequences of key proteins involved in AD pathogenesis are highly conserved between sheep and human. The processing of the amyloid-β (Aβ) protein is conserved between sheep and human, and sheep Aβ1-42/Aβ1-40 ratios in cerebrospinal fluid (CSF) are also very similar to human. In addition, total tau and neurofilament light levels in CSF are comparable with those found in human...
June 24, 2017: Neurobiology of Aging
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