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Neurobiology of Aging

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https://www.readbyqxmd.com/read/28735144/entorhinal-tau-pathology-disrupts-hippocampal-prefrontal-oscillatory-coupling-during-associative-learning
#1
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
#2
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/28732249/evaluating-alzheimer-s-disease-biomarkers-as-mediators-of-age-related-cognitive-decline
#3
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
#4
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/28716534/mutations-in-tyrobp-are-not-a-common-cause-of-dementia-in-a-turkish-cohort
#5
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/28666710/homozygous-alpha-synuclein-p-a53v-in-familial-parkinson-s-disease
#6
Hiroyo Yoshino, Makito Hirano, A Jon Stoessl, Yoko Imamichi, Aya Ikeda, Yuanzhe Li, Manabu Funayama, Ikuko Yamada, Yusaku Nakamura, Vesna Sossi, Matthew J Farrer, Kenya Nishioka, Nobutaka Hattori
We have assessed the frequency of alpha-synuclein (SNCA) mutations in Japanese patients with familial or sporadic Parkinson's disease (PD) and surveyed their associated clinical manifestations. We screened SNCA exon 3 in 988 patients without SNCA multiplications (430 with autosomal dominant PD and 558 with sporadic PD). We detected 1 patient harboring a homozygous SNCA p.A53V substitution albeit with an autosomal dominant pattern of disease inheritance (frequency 2/860 = 0.2%). The proband manifested slow and progressive parkinsonism at 55 years...
June 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28728889/cognitive-and-motor-functioning-in-elderly-glucocerebrosidase-mutation-carriers
#7
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
#8
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
https://www.readbyqxmd.com/read/28719855/high-fat-diet-and-aging-interact-to-produce-neuroinflammation-and-impair-hippocampal-and-amygdalar-dependent-memory
#9
Sarah J Spencer, Heather D'Angelo, Alita Soch, Linda R Watkins, Steven F Maier, Ruth M Barrientos
More Americans are consuming diets higher in saturated fats and refined sugars than ever before, and based on increasing obesity rates, this is a growing trend among older adults as well. While high saturated fat diet (HFD) consumption has been shown to sensitize the inflammatory response to a subsequent immune challenge in young adult rats, the inflammatory effect of HFD in the already-vulnerable aging brain has not yet been assessed. Here, we explored whether short-term (3 days) consumption of HFD would serve as a neuroinflammatory trigger in aging animals, leading to cognitive deficits...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28719854/clinically-silent-alzheimer-s-and-vascular-pathologies-influence-brain-networks-supporting-executive-function-in-healthy-older-adults
#10
Brian T Gold, Christopher A Brown, Jonathan G Hakun, Leslie M Shaw, John Q Trojanowski, Charles D Smith
Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer's disease (AD) pathology and cerebral white-matter hyperintensities (WMHs). Twenty-nine younger adults and 34 cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging was performed. Older adults further underwent lumbar cerebrospinal fluid draw for the assessment of AD pathology and FLAIR imaging for the assessment of WMHs...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28716533/novel-ubqln2-mutations-linked-to-amyotrophic-lateral-sclerosis-and-atypical-hereditary-spastic-paraplegia-phenotype-through-defective-hsp70-mediated-proteolysis
#11
Elisa Teyssou, Laura Chartier, Maria-Del-Mar Amador, Roselina Lam, Géraldine Lautrette, Marie Nicol, Selma Machat, Sandra Da Barroca, Carine Moigneu, Mathilde Mairey, Thierry Larmonier, Safaa Saker, Christelle Dussert, Sylvie Forlani, Bertrand Fontaine, Danielle Seilhean, Delphine Bohl, Séverine Boillée, Vincent Meininger, Philippe Couratier, François Salachas, Giovanni Stevanin, Stéphanie Millecamps
Mutations in UBQLN2 have been associated with rare cases of X-linked juvenile and adult forms of amyotrophic lateral sclerosis (ALS) and ALS linked to frontotemporal dementia (FTD). Here, we report 1 known (c.1489C>T, p.Pro497Ser, P497S) and 3 novel (c.1481C>T, p.Pro494Leu, P494L; c.1498C>T, p.Pro500Ser, P500S; and c.1516C>G, p.Pro506Ala, P506A) missense mutations in the PXX domain of UBQLN2 in familial motor neuron diseases including ALS and spastic paraplegia (SP). A novel missense mutation (c...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28709721/screening-for-tmem230-mutations-in-young-onset-parkinson-s-disease
#12
Dongrui Ma, Jia Nee Foo, Ebonne Yulin Ng, Yi Zhao, Jian-Jun Liu, Eng King Tan
TMEM230 gene mutations have been reported to be linked with Parkinson's disease (PD) recently. To investigate the prevalence of this gene in southeastern Chinese patients with PD, whole exome sequencing was performed in young-onset and familial PD patients and healthy controls in our Asian population. One heterozygous missense p.Phe121Ser mutation was detected in a healthy 76-year-old control subject and no other TMEM230 mutations were found in PD patients and controls. These data suggest that TMEM230 mutation might be a rare cause of Chinese familial and sporadic PD patients and a larger sample size will be needed to evaluate the association of TMEM230 polymorphic variants with PD...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28716532/multivariate-analyses-of-peripheral-blood-leukocyte-transcripts-distinguish-alzheimer-s-parkinson-s-control-and-those-at-risk-for-developing-alzheimer-s
#13
Elaine Delvaux, Diego Mastroeni, Jennifer Nolz, Nienwen Chow, Marwan Sabbagh, Richard J Caselli, Eric M Reiman, Frederick J Marshall, Paul D Coleman
The need for a reliable, simple, and inexpensive blood test for Alzheimer's disease (AD) suitable for use in a primary care setting is widely recognized. This has led to a large number of publications describing blood tests for AD, which have, for the most part, not been replicable. We have chosen to examine transcripts expressed by the cellular, leukocyte compartment of blood. We have used hypothesis-based cDNA arrays and quantitative PCR to quantify the expression of selected sets of genes followed by multivariate analyses in multiple independent samples...
June 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28709720/burden-of-rare-variants-in-als-genes-influences-survival-in-familial-and-sporadic-als
#14
Shirley Yin-Yu Pang, Jacob Shujui Hsu, Kay-Cheong Teo, Yan Li, Michelle H W Kung, Kathryn S E Cheah, Danny Chan, Kenneth M C Cheung, Miaoxin Li, Pak-Chung Sham, Shu-Leong Ho
Genetic variants are implicated in the development of amyotrophic lateral sclerosis (ALS), but it is unclear whether the burden of rare variants in ALS genes has an effect on survival. We performed whole genome sequencing on 8 familial ALS (FALS) patients with superoxide dismutase 1 (SOD1) mutation and whole exome sequencing on 46 sporadic ALS (SALS) patients living in Hong Kong and found that 67% had at least 1 rare variant in the exons of 40 ALS genes; 22% had 2 or more. Patients with 2 or more rare variants had lower probability of survival than patients with 0 or 1 variant (p = 0...
June 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28708977/relative-cortico-subcortical-shift-in-brain-activity-but-preserved-training-induced-neural-modulation-in-older-adults-during-bimanual-motor-learning
#15
Thiago Santos Monteiro, Iseult A M Beets, Matthieu P Boisgontier, Jolien Gooijers, Lisa Pauwels, Sima Chalavi, Brad King, Geneviève Albouy, Stephan P Swinnen
To study age-related differences in neural activation during motor learning, functional magnetic resonance imaging scans were acquired from 25 young (mean 21.5-year old) and 18 older adults (mean 68.6-year old) while performing a bimanual coordination task before (pretest) and after (posttest) a 2-week training intervention on the task. We studied whether task-related brain activity and training-induced brain activation changes differed between age groups, particularly with respect to the hyperactivation typically observed in older adults...
June 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28705468/association-of-anti-inflammatory-cytokine-il10-polymorphisms-with-motoric-cognitive-risk-syndrome-in-an-ashkenazi-jewish-population
#16
Sanish Sathyan, Nir Barzilai, Gil Atzmon, Sofiya Milman, Emmeline Ayers, Joe Verghese
Motoric cognitive risk (MCR) syndrome is a newly described predementia syndrome characterized by the presence of cognitive complaints and slow gait, which is associated with increased risk of conversion to dementia. The underlying biological mechanisms for MCR have not yet been established. Neuroinflammation mediated through cytokines plays a pivotal role in the pathogenesis of dementia. Hence, our objective was to prospectively examine whether variations in cytokine genes (CRP, IFNG, IL1A, IL1B, IL4, IL6, IL10, IL18, TNF, and IL12A) play a role in MCR incidence in 530 community-dwelling Ashkenazi Jewish adults aged 65 years and older without MCR or dementia at baseline enrolled in the LonGenity study...
June 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28697377/absence-of-regulator-of-g-protein-signaling-4-does-not-protect-against-dopamine-neuron-dysfunction-and-injury-in-the-mouse-6-hydroxydopamine-lesion-model-of-parkinson-s-disease
#17
Amer Ashrafi, Pierre Garcia, Heike Kollmus, Klaus Schughart, Antonio Del Sol, Manuel Buttini, Enrico Glaab
Regulator of G-protein signaling 4 (RGS4), a member of the RGS family of proteins that inactivate G-proteins, has gained interest as a potential drug target for neurological disorders, such as epilepsy and Parkinson's disease (PD). In the case of PD, the main current options for alleviating motor symptoms are dopamine replacement therapies, which have limitations because of side effects and reduced effectiveness over the long term. Research on new nondopaminergic PD drug targets has indicated that inhibition of RGS4 could be an effective adjuvant treatment option...
June 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28692878/sex-specific-association-of-sex-hormones-and-gonadotropins-with-brain-amyloid-and-hippocampal-neurodegeneration
#18
Jun Ho Lee, Min Soo Byun, Dahyun Yi, Young Min Choe, Hyo Jung Choi, Hyewon Baek, Bo Kyung Sohn, Jun-Young Lee, Hyun Jung Kim, Jee Wook Kim, Younghwa Lee, Yu Kyeong Kim, Chul-Ho Sohn, Jong Inn Woo, Dong Young Lee
This study aimed to examine the sex-specific association between serum sex hormones and gonadotropins and the cerebral beta-amyloid (Aβ) burden and hippocampal neurodegeneration in subjects with normal cognition and impaired cognition. Two hundred sixty-five older subjects received clinical assessments, serum measurements of sex hormones, gonadotropins, (11)C-Pittsburgh compound B-positron emission tomography, and magnetic resonance imaging. In females, higher free testosterone and gonadotropin levels were associated with lower cerebral Aβ positivity...
June 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28692877/association-between-cerebrospinal-fluid-and-plasma-neurodegeneration-biomarkers-with-brain-atrophy-in-alzheimer-s-disease
#19
Joana B Pereira, Eric Westman, Oskar Hansson
The aggregation and deposition of amyloid-β (Aβ) peptides into plaques is an early event in Alzheimer's disease (AD), which is followed by different aspects of neurodegeneration that can be measured in the cerebrospinal fluid (CSF) or plasma using neurofilament light (NFL), neurogranin (Ng), total Tau (T-Tau), and phosphorylated tau (P-Tau) levels. The relationship between these biomarkers and regional brain atrophy across the different stages of AD remains largely unexplored. In this study, we assessed whether NFL, Ng, T-Tau, and P-Tau levels in CSF and NFL in plasma are associated with cortical thinning and subcortical volume loss in cognitively normal, mild cognitive impairment, and AD subjects with and without Aβ pathology...
June 17, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28688899/central-insulin-dysregulation-and-energy-dyshomeostasis-in-two-mouse-models-of-alzheimer-s-disease
#20
Ramon Velazquez, An Tran, Egide Ishimwe, Larry Denner, Nikhil Dave, Salvatore Oddo, Kelly T Dineley
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are not known, several risk factors have been identified. Among these, type two diabetes (T2D), a chronic metabolic disease, is one of the most prevalent risk factors for AD. Insulin resistance, which is associated with T2D, is defined as diminished or absent insulin signaling and is reflected by peripheral blood hyperglycemia and impaired glucose clearance. In this study, we used complementary approaches to probe for peripheral insulin resistance, central nervous system (CNS) insulin sensitivity and energy homeostasis in Tg2576 and 3xTg-AD mice, two widely used animal models of AD...
June 17, 2017: Neurobiology of Aging
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