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Neurobiology of Aging

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https://www.readbyqxmd.com/read/29050849/neuronal-and-behavioral-effects-of-multi-day-brain-stimulation-and-memory-training
#1
Daria Antonenko, Nadine Külzow, Angelica Sousa, Kristin Prehn, Ulrike Grittner, Agnes Flöel
Strategies for memory enhancement, especially for the older population, are of great scientific and public interest. Here, we aimed at investigating neuronal and behavioral effects of transcranial direct current stimulation (tDCS) paired with memory training. Young and older adults were trained on an object-location-memory task on 3 consecutive days with either anodal or sham tDCS. Recall performance was assessed immediately after training, 1 day and 1 month later, as well as performance on trained function and transfer task...
September 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29042130/a-decay-of-the-adaptive-capacity-of-the-unfolded-protein-response-exacerbates-alzheimer-s-disease
#2
Yannis Gerakis, Claudio Hetz
Alterations in the buffering capacity of the proteostasis network are a salient feature of Alzheimer's disease, associated with the occurrence of chronic endoplasmic reticulum (ER) stress. To cope with ER stress, cells activate the unfolded protein response (UPR), a signal transduction pathway that enforces adaptive programs through the induction of transcription factors such as X-box binding protein 1 (XBP1). A new study by Marcora et al used a fly model to study amyloid β pathogenesis in the secretory pathway of neurons...
September 22, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29035751/intercellular-transfer-of-pathogenic-%C3%AE-synuclein-by-extracellular-vesicles-is-induced-by-the-lipid-peroxidation-product-4-hydroxynonenal
#3
Shi Zhang, Erez Eitan, Tsung-Yu Wu, Mark P Mattson
Parkinson's disease (PD) is characterized by accumulations of toxic α-synuclein aggregates in vulnerable neuronal populations in the brainstem, midbrain, and cerebral cortex. Recent findings suggest that α-synuclein pathology can be propagated transneuronally, but the underlying molecular mechanisms are unknown. Advances in the genetics of rare early-onset familial PD indicate that increased production and/or reduced autophagic clearance of α-synuclein can cause PD. The cause of the most common late-onset PD is unclear, but may involve metabolic compromise and oxidative stress upstream of α-synuclein accumulation...
September 22, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29032192/age-dependent-association-of-thyroid-function-with-brain-morphology-and-microstructural-organization-evidence-from-brain-imaging
#4
Layal Chaker, Lotte G M Cremers, Tim I M Korevaar, Marius de Groot, Abbas Dehghan, Oscar H Franco, Wiro J Niessen, M Arfan Ikram, Robin P Peeters, Meike W Vernooij
Thyroid hormone (TH) is crucial during neurodevelopment, but high levels of TH have been linked to neurodegenerative disorders. No data on the association of thyroid function with brain imaging in the general population are available. We therefore investigated the association of thyroid-stimulating hormone and free thyroxine (FT4) with magnetic resonance imaging (MRI)-derived total intracranial volume, brain tissue volumes, and diffusion tensor imaging measures of white matter microstructure in 4683 dementia- and stroke-free participants (mean age 60...
September 22, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28946017/par3-and-apkc-regulate-bace1-endosome-to-tgn-trafficking-through%C3%A2-pacs1
#5
Miao Sun, Huaye Zhang
The cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) is the rate-limiting step in beta amyloid generation during Alzheimer's disease (AD) pathogenesis. In AD brains, BACE1 is abnormally accumulated in endocytic compartments, where the acidic pH is optimal for its activity. However, mechanisms regulating the endosome-to-trans-Golgi network (TGN) retrieval of BACE1 remain unclear. Here, we show that partitioning defective 3 (Par3) facilitates BACE1 retrograde trafficking from endosomes to the TGN...
September 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29040871/gray-matter-networks-and-clinical-progression-in-subjects-with-predementia-alzheimer-s-disease
#6
Betty M Tijms, Mara Ten Kate, Alida A Gouw, Andreas Borta, Sander Verfaillie, Charlotte E Teunissen, Philip Scheltens, Frederik Barkhof, Wiesje M van der Flier
We studied whether gray matter network parameters are associated with rate of clinical progression in nondemented subjects who have abnormal amyloid markers in the cerebrospinal fluid (CSF), that is, predementia Alzheimer's disease. Nondemented subjects (62 with subjective cognitive decline; 160 with mild cognitive impairment (MCI); age = 68 ± 8 years; Mini-Mental State Examination (MMSE) = 28 ± 2.4) were selected from the Amsterdam Dementia Cohort when they had abnormal amyloid in CSF (<640 pg/mL)...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29040870/parkin-absence-accelerates-microtubule-aging-in-dopaminergic-neurons
#7
Daniele Cartelli, Alida Amadeo, Alessandra Maria Calogero, Francesca Vittoria Marialuisa Casagrande, Carmelita De Gregorio, Mariarosa Gioria, Naoko Kuzumaki, Ilaria Costa, Jenny Sassone, Andrea Ciammola, Nobutaka Hattori, Hideyuki Okano, Stefano Goldwurm, Laurent Roybon, Gianni Pezzoli, Graziella Cappelletti
Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29031088/probing-the-correlation-of-neuronal-loss-neurofibrillary-tangles-and-cell-death-markers-across-the-alzheimer-s-disease-braak-stages-a-quantitative-study-in-humans
#8
Panos Theofilas, Alexander J Ehrenberg, Austin Nguy, Julia M Thackrey, Sara Dunlop, Maria B Mejia, Ana T Alho, Renata Elaine Paraizo Leite, Roberta Diehl Rodriguez, Claudia K Suemoto, Camila F Nascimento, Marcus Chin, Daniel Medina-Cleghorn, Ana Maria Cuervo, Michelle Arkin, William W Seeley, Bruce L Miller, Ricardo Nitrini, Carlos Augusto Pasqualucci, Wilson Jacob Filho, Udo Rueb, John Neuhaus, Helmut Heinsen, Lea T Grinberg
Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29029762/thinner-cortex-in-patients-with-subjective-cognitive-decline-is-associated-with-steeper-decline-of-memory
#9
Sander C J Verfaillie, Rosalinde E Slot, Betty M Tijms, Femke Bouwman, Marije R Benedictus, Jozefien M Overbeek, Teddy Koene, Hugo Vrenken, Philip Scheltens, Frederik Barkhof, Wiesje M van der Flier
We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2-8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini-Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29032190/transient-increase-in-sapp%C3%AE-secretion-in-response-to-a%C3%AE-1-42-oligomers-an-attempt-of-neuronal-self-defense
#10
Christiane Rose, Emilie Dorard, Mickael Audrain, Lucie Gorisse-Hussonnois, Nathalie Cartier, Jérome Braudeau, Bernadette Allinquant
Amyloid precursor protein (APP), a key molecule of Alzheimer disease, is metabolized in 2 antagonist pathways generating the soluble APP alpha (sAPPα) having neuroprotective properties and the beta amyloid (Aβ) peptide at the origin of neurotoxic oligomers, particularly Aβ1-42. Whether extracellular Aβ1-42 oligomers modulate the formation and secretion of sAPPα is not known. We report here that the addition of Aβ1-42 oligomers to primary cortical neurons induced a transient increase in α-secretase activity and secreted sAPPα 6-9 hours later...
September 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29032894/atypical-pkc-pkc%C3%AE-%C3%AE-activates-%C3%AE-secretase-and-increases-a%C3%AE-1-40-42-and-phospho-tau-in-mouse-brain-and-isolated-neuronal-cells-and-may-link-hyperinsulinemia-and-other-apkc-activators-to-development-of-pathological-and-memory-abnormalities-in-alzheimer-s-disease
#11
Mini P Sajan, Barbara C Hansen, Margaret G Higgs, C Ron Kahn, Ursula Braun, Michael Leitges, Collin R Park, David M Diamond, Robert V Farese
Hyperinsulinemia activates brain Akt and PKC-λ/ι and increases Aβ1-40/42 and phospho-tau in insulin-resistant animals. Here, we examined underlying mechanisms in mice, neuronal cells, and mouse hippocampal slices. Like Aβ1-40/42, β-secretase activity was increased in insulin-resistant mice and monkeys. In insulin-resistant mice, inhibition of hepatic PKC-λ/ι sufficient to correct hepatic abnormalities and hyperinsulinemia simultaneously reversed increases in Akt, atypical protein kinase C (aPKC), β-secretase, and Aβ1-40/42, and restored acute Akt activation...
September 15, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29031089/17%C3%AE-estradiol-regulates-the-rna-binding-protein-nova1-which-then-regulates-the-alternative-splicing-of-estrogen-receptor-%C3%AE-in-the-aging-female-rat-brain
#12
Cody L Shults, Caitlin B Dingwall, Chun K Kim, Elena Pinceti, Yathindar S Rao, Toni R Pak
Alternative RNA splicing results in the translation of diverse protein products arising from a common nucleotide sequence. These alternative protein products are often functional and can have widely divergent actions from the canonical protein. Studies in humans and other vertebrate animals have demonstrated that alternative splicing events increase with advanced age, sometimes resulting in pathological consequences. Menopause represents a critical transition for women, where the beneficial effects of estrogens are no longer evident; therefore, factors underlying increased pathological conditions in women are confounded by the dual factors of aging and declining estrogens...
September 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28992987/the-resting-perfusion-pattern-associates-with-functional-decline-in-type-2-diabetes
#13
Weiying Dai, Wenna Duan, Freddy J Alfaro, Anna Gavrieli, Fotini Kourtelidis, Vera Novak
We investigated the relationships between cerebral blood flow (CBF), cognitive, and mobility decline in type 2 diabetes mellitus (T2DM) over a 2-year period. Seventy-three participants (41 T2DM and 32 controls) were evaluated using volumetric CBF with arterial spin labeling perfusion magnetic resonance imaging at baseline and at the 2-year follow-up. Regions with significant CBF differences between T2DM participants and controls at baseline were detected using voxel-wise analysis. Correlation analysis was performed to investigate the association between regional CBF and cognitive or mobility performance over the 2-year span...
September 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28974335/retinal-neurodegeneration-and-brain-mri-markers-the-rotterdam-study
#14
Unal Mutlu, Pieter W M Bonnemaijer, M Arfan Ikram, Johanna M Colijn, Lotte G M Cremers, Gabriëlle H S Buitendijk, Johannes R Vingerling, Wiro J Niessen, Meike W Vernooij, Caroline C W Klaver, M Kamran Ikram
We investigated the association of specific retinal sublayer thicknesses on optical coherence tomography (OCT) with brain magnetic resonance imaging (MRI) markers. We included 2124 persons (mean age 67.0 years; 56% women) from the Rotterdam Study who had gradable retinal OCT images and brain MRI scans. Thickness of retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer were measured on OCT images. Volumetric, microstructural, and focal markers of brain tissue were assessed on MRI...
September 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28968586/cognitive-reserve-and-long-term-change-in-cognition-in-aging-and-preclinical-alzheimer-s-disease
#15
Anja Soldan, Corinne Pettigrew, Qing Cai, Jiangxia Wang, Mei-Cheng Wang, Abhay Moghekar, Michael I Miller, Marilyn Albert
We examined if baseline levels of cognitive reserve (CR) and of Alzheimer's disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n = 303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed mild cognitive impairment (MCI) or dementia due to AD. CR was indexed by years of education, reading, and vocabulary measures. AD biomarkers were measured with a composite score composed of measures of amyloid, phosphorylated tau, and neurodegeneration...
September 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29033165/molecular-epidemiological-study-of-familial-amyotrophic-lateral-sclerosis-in-japanese-population-by-whole-exome-sequencing-and-identification-of-novel-hnrnpa1-mutation
#16
Hiroya Naruse, Hiroyuki Ishiura, Jun Mitsui, Hidetoshi Date, Yuji Takahashi, Takashi Matsukawa, Masaki Tanaka, Akiko Ishii, Akira Tamaoka, Keiichi Hokkoku, Masahiro Sonoo, Mari Segawa, Yoshikazu Ugawa, Koichiro Doi, Jun Yoshimura, Shinichi Morishita, Jun Goto, Shoji Tsuji
To elucidate the genetic epidemiology of familial amyotrophic lateral sclerosis (FALS) in the Japanese population, we conducted whole-exome sequencing analysis of 30 FALS families in whom causative mutations have not been identified in previous studies. Consequently, whole-exome sequencing analysis revealed novel mutations in HNRNPA1, TBK1, and VCP. Taken together with our previous results of mutational analyses by direct nucleotide sequencing analysis, a microarray-based resequencing method, or repeat-primed PCR analysis, causative mutations were identified in 41 of the 68 families (60...
September 6, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29032191/aging-and-a-genetic-kibra-polymorphism-interactively-affect-feedback-and-observation-based-probabilistic-classification-learning
#17
Nicolas W Schuck, Jessica R Petok, Martijn Meeter, Brit-Maren M Schjeide, Julia Schröder, Lars Bertram, Mark A Gluck, Shu-Chen Li
Probabilistic category learning involves complex interactions between the hippocampus and striatum that may depend on whether acquisition occurs via feedback or observation. Little is known about how healthy aging affects these processes. We tested whether age-related behavioral differences in probabilistic category learning from feedback or observation depend on a genetic factor known to influence individual differences in hippocampal function, the KIBRA gene (single nucleotide polymorphism rs17070145). Results showed comparable age-related performance impairments in observational as well as feedback-based learning...
September 5, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28946019/dynamic-range-in-bold-modulation-lifespan-aging-trajectories-and-association-with-performance
#18
Kristen M Kennedy, Maria A Boylan, Jenny R Rieck, Chris M Foster, Karen M Rodrigue
Alteration of dynamic range of modulation to cognitive difficulty has been proposed as a salient predictor of cognitive aging. Here, we examine in 171 adults (aged 20-94 years) the effects of age on dynamic modulation of blood oxygenation-level dependent activation to difficulty in parametrically increasing working memory (WM) load (0-, 2-, 3-, and 4-back conditions). First, we examined parametric increases and decreases in activation to increasing WM load (positive modulation effect and negative modulation effect)...
September 5, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28946018/decline-of-prefrontal-cortical-mediated-executive-functions-but-attenuated-delay-discounting-in-aged-fischer-344%C3%A2-%C3%A3-brown-norway-hybrid-rats
#19
Caesar M Hernandez, Lauren M Vetere, Caitlin A Orsini, Joseph A McQuail, Andrew P Maurer, Sara N Burke, Barry Setlow, Jennifer L Bizon
Despite the fact that prefrontal cortex (PFC) function declines with age, aged individuals generally show an enhanced ability to delay gratification, as evident by less discounting of delayed rewards in intertemporal choice tasks. The present study was designed to evaluate relationships between 2 aspects of PFC-dependent cognition (working memory and cognitive flexibility) and intertemporal choice in young (6 months) and aged (24 months) Fischer 344 × brown Norway F1 hybrid rats. Rats were also evaluated for motivation to earn rewards using a progressive ratio task...
September 5, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28941727/intravenous-treatment-with-human-recombinant-apoa-i-milano-reduces-beta-amyloid-cerebral-deposition-in-the-app23-transgenic-mouse-model-of-alzheimer-s-disease
#20
Sofía Fernández-de Retana, Alex Montañola, Paula Marazuela, Maialen De La Cuesta, Aina Batlle, Marc Fatar, Saskia Grudzenski, Joan Montaner, Mar Hernández-Guillamon
Beyond the crucial role of apolipoprotein A-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in beta amyloid (Aβ)-related neuropathologies. ApoA-I-Milano (M) is a mutated variant, which showed increased vasoprotective properties compared to ApoA-I-wild type in models of atherosclerosis and cardiovascular damage. We speculated that ApoA-I-M may also protect Aβ-affected vasculature and reverse some of the pathological features associated with Alzheimer's disease (AD)...
September 5, 2017: Neurobiology of Aging
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