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https://www.readbyqxmd.com/read/28344547/app-function-and-lipids-a-bidirectional-link
#1
REVIEW
Marcus O W Grimm, Janine Mett, Heike S Grimm, Tobias Hartmann
Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer's disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28339396/modulation-of-a%C3%AE-pp-and-gsk3%C3%AE-by-endoplasmic-reticulum-stress-and-involvement-in-alzheimer-s-disease
#2
Xin-Jun Liu, Jun Wei, Ying-Hui Shang, Han-Chang Huang, Feng-Xue Lao
Alzheimer's disease (AD) is a dementia disease with neuronal loss and synaptic impairment. This impairment is caused, at least partly, by the generation of two main AD hallmarks, namely the hyperphosphorylated tau protein comprising neurofibrillary tangles and senile plaques containing amyloid-β (Aβ) peptides. The amyloid-β protein precursor (AβPP) and glycogen synthase kinase-3β (GSK3β) are two main proteins associated with AD and are closely correlated with these hallmarks. Recently, both of the proteins were reported to be modulated by endoplasmic reticulum stress (ERS) and are involved in the pathogenesis of AD...
March 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28337257/subcutaneous-liraglutide-ameliorates-methylglyoxal-induced-alzheimer-like-tau-pathology-and-cognitive-impairment-by-modulating-tau-hyperphosphorylation-and-glycogen-synthase-kinase-3%C3%AE
#3
Liqin Qi, Zhou Chen, Yanping Wang, Xiaoying Liu, Xiaohong Liu, Linfang Ke, Zhongjie Zheng, Xiaowei Lin, Yu Zhou, Lijuan Wu, Libin Liu
Memory deterioration and synapse damage with accumulation of β-amyloid and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). Methylglyoxal (MG), a key intermediate of glucose metabolism, is elevated in AD brains and modifies Aβ42, increasing misfolding and leading to the accumulation of senile plaques. Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is neurotrophic and neuroprotective. However, whether liraglutide can protect against AD-like memory-related deficits and tau hyperphosphorylation caused by MG in vivo is not known...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337142/icariside-ii-effectively-reduces-spatial-learning-and-memory-impairments-in-alzheimer-s-disease-model-mice-targeting-beta-amyloid-production
#4
Lingli Yan, Yuanyuan Deng, Jianmei Gao, Yuangui Liu, Fei Li, Jingshan Shi, Qihai Gong
Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer's disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28336433/early-stage-reduction-of-the-dendritic-complexity-in-basolateral-amygdala-of-a-transgenic-mouse-model-of-alzheimer-s-disease
#5
Congdi Guo, Ben Long, Yarong Hu, Jing Yuan, Hui Gong, Xiangning Li
Alzheimer's disease is a representative age-related neurodegenerative disease that could result in loss of memory and cognitive deficiency. However, the precise onset time of Alzheimer's disease affecting neuronal circuits and the mechanisms underlying the changes are not clearly known. To address the neuroanatomical changes during the early pathologic developing process, we acquired the neuronal morphological characterization of AD in APP/PS1 double-transgenic mice using the Micro-Optical Sectioning Tomography system...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28334939/association-between-tau-deposition-and-antecedent-amyloid-%C3%AE-accumulation-rates-in-normal-and-early-symptomatic-individuals
#6
Duygu Tosun, Susan Landau, Paul S Aisen, Ronald C Petersen, Mark Mintun, William Jagust, Michael W Weiner
A long-term goal of our field is to determine the sequence of pathological events, which ultimately lead to cognitive decline and dementia. In this study, we first assessed the patterns of brain tau tangle accumulation (measured with the positron emission tomography tracer 18F-AV-1451) associated with well-established Alzheimer's disease factors in a cohort including cognitively healthy elderly individuals and individuals at early symptomatic stages of Alzheimer's disease. We then explored highly associated patterns of greater 18F-AV-1451 binding and increased annualized change in cortical amyloid-β plaques measured as florbetapir positron emission tomography binding antecedent to 18F-AV-1451 positron emission tomography scans, and to what extent these multimodal pattern associations explained the variance in cognitive performance and clinical outcome measures, independently and jointly...
March 17, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334103/neuronal-and-peripheral-pentraxins-modify-glutamate-release-and-may-interact-in-blood-brain-barrier-failure
#7
Damian M Cummings, Tiffanie A Benway, Hinze Ho, Angelo Tedoldi, Monica M Fernandes Freitas, Lion Shahab, Christina E Murray, Angela Richard-Loendt, Sebastian Brandner, Tammaryn Lashley, Dervis A Salih, Frances A Edwards
Neuronal pentraxin 1 (NPTX1) has been implicated in Alzheimer's disease, being present in and around dystrophic neurons in plaques, affecting glutamatergic transmission postsynaptically and mediating effects of amyloidβ. Here, we confirm the presence of NPTX1 around plaques in postmortem Alzheimer's disease brain and report that acutely applied human NPTX1 increases paired-pulse ratio at mouse CA3-CA1 hippocampal synapses, indicating a decrease in glutamate release. In contrast, chronic exposure to NPTX1, NPTX2, or NPTX receptor decreases paired-pulse ratio, mimicking some of the earliest changes in mice expressing familial Alzheimer's disease genes...
February 23, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28332351/metabolism-centric-overview-of-the-pathogenesis-of-alzheimer-s-disease
#8
REVIEW
Somang Kang, Yong Ho Lee, Jong Eun Lee
Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia. AD is characterized by the extracellular amyloid beta (Aβ) plaques and intraneuronal deposits of neurofibrillary tangles (NFTs). Recently, as aging has become a familiar phenomenon around the world, patients with AD are increasing in number. Thus, many researchers are working toward finding effective therapeutics for AD focused on Aβ hypothesis, although there has been no success yet. In this review paper, we suggest that AD is a metabolic disease and that we should focus on metabolites that are affected by metabolic alterations to find effective therapeutics for AD...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28331770/traditional-food-items-in-ogimi-okinawa-l-serine-content-and-the-potential-for-neuroprotection
#9
REVIEW
Paul Alan Cox, James S Metcalf
PURPOSE OF REVIEW: Ogimi village is renowned for its aging population. We sought to determine if the l-serine content of their diet could account for their neurological health. RECENT FINDINGS: The most frequently consumed food items, including tofu and seaweeds, are rich in the dietary amino acid l-serine. l-serine content of the Ogimi diet >8 grams/day for Ogimi women significantly exceeds the average American dietary intake of 2.5 grams/day for women >70 years old...
2017: Current Nutrition Reports
https://www.readbyqxmd.com/read/28330719/nicotinamide-mononucleotide-inhibits-jnk-activation-to-reverse-alzheimer-disease
#10
Zhiwen Yao, Wenhao Yang, Zhiqiang Gao, Peng Jia
Amyloid-β (Aβ) oligomers have been accepted as major neurotoxic agents in the therapy of Alzheimer's disease (AD). It has been shown that the activity of nicotinamide adenine dinucleotide (NAD+) is related with the decline of Aβ toxicity in AD. Nicotinamide mononucleotide (NMN), the important precursor of NAD+, is produced during the reaction of nicotinamide phosphoribosyl transferase (Nampt). This study aimed to figure out the potential therapeutic effects of NMN and its underlying mechanisms in APPswe/PS1dE9 (AD-Tg) mice...
March 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28326436/reference-region-selection-and-the-association-between-the-rate-of-amyloid-accumulation-over-time-and-the-baseline-amyloid-burden
#11
Janusch Blautzik, Matthias Brendel, Julia Sauerbeck, Sebastian Kotz, Franziska Scheiwein, Peter Bartenstein, John Seibyl, Axel Rominger
Relative quantitative analysis of amyloid plaque burden in Alzheimer's disease (AD) patients can be reported as standardized uptake value ratio (SUVR) from positron emission tomography (PET). Here, the SUVR is the ratio of the mean amyloid radioligand retention in a composite (COMP) neocortical volume of interest (VOI) to that in a reference VOI, such as the cerebellum, brainstem (BST)/pons, or white matter (WM). Some longitudinal PET investigations show that the rate of amyloid accumulation to follow-up has an inverted U relationship with baseline amyloid SUVR relative to cerebellar or brainstem/pons reference VOIs...
March 22, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28324600/light-sheet-fluorescence-microscopy-chemical-clearing-and-labeling-protocols-for-ultramicroscopy
#12
Nina Jährling, Klaus Becker, Saiedeh Saghafi, Hans-Ulrich Dodt
Light-sheet microscopy is an effective technique in neuroscience, developmental biology, and cancer research for visualizing and analyzing cellular networks and whole organs in three dimensions. Because this technique requires specimens to be translucent they commonly have to be cleared before microscopy inspection. Here, we provide 3DISCO based protocols for preparing cleared samples of immuno-stained neural networks, lectin-labeled vascular networks, and Methoxy-X04 labeled beta-amyloid plaques in mice. 3DISCO utilizes the lipophilic solvents tetrahydrofuran (THF) and dibenzylether (DBE) for dehydration and successive clearing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28323038/monocular-denervation-of-visual-nuclei-modulates-app-processing-and-sapp%C3%AE-production-a-possible-role-on-neural-plasticity
#13
Juliana Ferreira Vasques, Pedro Vinícius Bastos Heringer, Renata Guedes de Jesus Gonçalves, Paula Campello-Costa, Claudio Alberto Serfaty, Adriana da Cunha Faria-Melibeu
Amyloid precursor protein (APP) is essential to physiological processes such as synapse formation and neural plasticity. Sequential proteolysis of APP by beta- and gamma-secretases generates amyloid-beta peptide (Aβ), the main component of senile plaques in Alzheimer Disease. Alternative APP cleavage by alpha-secretase occurs within Aβ domain, releasing soluble α-APP (sAPPα), a neurotrophic fragment. Among other functions, sAPPα is important to synaptogenesis, neural survival and axonal growth. APP and sAPPα levels are increased in models of neuroplasticity, which suggests an important role for APP and its metabolites, especially sAPPα, in the rearranging brain...
March 16, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28322283/susceptibility-to-neurofibrillary-tangles-role-of-the-ptprd-locus-and-limited-pleiotropy-with-other-neuropathologies
#14
L B Chibnik, C C White, S Mukherjee, T Raj, L Yu, E B Larson, T J Montine, C D Keene, J Sonnen, J A Schneider, P K Crane, J M Shulman, D A Bennett, P L De Jager
Tauopathies, including Alzheimer's disease (AD) and other neurodegenerative conditions, are defined by a pathological hallmark: neurofibrillary tangles (NFTs). NFT accumulation is thought to be closely linked to cognitive decline in AD. Here, we perform a genome-wide association study for NFT pathologic burden and report the association of the PTPRD locus (rs560380, P=3.8 × 10(-8)) in 909 prospective autopsies. The association is replicated in an independent data set of 369 autopsies. The association of PTPRD with NFT is not dependent on the accumulation of amyloid pathology...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28322204/cognitive-decline-associated-with-pathological-burden-in-primary-age-related-tauopathy
#15
Kyra S Jefferson-George, David A Wolk, Edward B Lee, Corey T McMillan
INTRODUCTION: Primary age-related tauopathy (PART) is a neuropathological diagnosis characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. Although most individuals over 50 years of age have evidence of NFTs, the clinical and cognitive consequences of PART are not known. METHODS: We evaluated 226 neuropathologically confirmed PART cases from the National Alzheimer's Coordinating Center database who participated in a total of 846 longitudinal neuropsychological assessments from the Alzheimer's Disease Center program's Uniform Data Set...
March 16, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28322202/genetic-epistasis-regulates-amyloid-deposition-in-resilient-aging
#16
Daniel Felsky, Jishu Xu, Lori Chibnik, Julie Schneider, Jo Knight, James L Kennedy, David A Bennett, Philip L De Jager, Aristotle N Voineskos
INTRODUCTION: The brain-derived neurotrophic factor (BDNF) interacts with important genetic Alzheimer's disease (AD) risk factors. Specifically, variants within the SORL1 gene determine BDNF's ability to reduce amyloid β (Aβ) in vitro. We sought to test whether functional BDNF variation interacts with SORL1 genotypes to influence expression and downstream AD-related processes in humans. METHODS: We analyzed postmortem brain RNA sequencing and neuropathological data for 441 subjects from the Religious Orders Study/Memory and Aging Project and molecular and structural neuroimaging data for 1285 subjects from the Alzheimer's Disease Neuroimaging Initiative...
March 16, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28321471/feasibility-of-in-vivo-18-f-florbetaben-pet-mr-imaging-of-human-carotid-amyloid-%C3%AE
#17
Jan Bucerius, Henryk Barthel, Solveig Tiepolt, Peter Werner, Judith C Sluimer, Joachim E Wildberger, Marianne Patt, Swen Hesse, Hermann-Josef Gertz, Erik A L Biessen, Felix M Mottaghy, Osama Sabri
PURPOSE: Amyloid-beta (Aβ) peptides are involved in the inflammatory pathology of atherosclerosis. (18)F-Florbetaben is a PET tracer for clinical imaging of cerebral Aβ plaques in Alzheimer's disease (AD). We sought to determine whether specific uptake of (18)F-florbetaben in the carotid arteries can be identified using a fully integrated hybrid PET/MRI system and whether this uptake is associated with clinical cardiovascular disease (CVD) risk factors. METHODS: Carotid (18)F-florbetaben uptake was quantified as the mean of the maximum target-to-background ratio (meanTBRmax) in 40 cognitively impaired subjects (age 68...
March 21, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28320441/decreased-cortical-fadd-protein-is-associated-with-clinical-dementia-and-cognitive-decline-in-an-elderly-community-sample
#18
Alfredo Ramos-Miguel, Jesús A García-Sevilla, Alasdair M Barr, Thomas A Bayer, Peter Falkai, Sue E Leurgans, Julie A Schneider, David A Bennett, William G Honer, M Julia García-Fuster
BACKGROUND: FADD (Fas-associated death domain) adaptor is a crucial protein involved in the induction of cell death but also mediates non-apoptotic actions via a phosphorylated form (p-Ser194-FADD). This study investigated the possible association of FADD forms with age-related neuropathologies, cognitive function, and the odds of dementia in an elderly community sample. METHODS: FADD forms were quantified by western blot analysis in dorsolateral prefrontal cortex (DLPFC) samples from a large cohort of participants in a community-based aging study (Memory and Aging Project, MAP), experiencing no-(NCI, n = 51) or mild-(MCI, n = 42) cognitive impairment, or dementia (n = 57)...
March 20, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28320296/biological-basis-for-amyloidogenesis-in-alzheimer-s-disease
#19
REVIEW
T V Andreeva, W J Lukiw, E I Rogaev
Certain cellular proteins normally soluble in the living organism under certain conditions form aggregates with a specific cross-β sheet structure called amyloid. These intra- or extracellular insoluble aggregates (fibers or plaques) are hallmarks of many neurodegenerative pathologies including Alzheimer's disease (AD), Huntington's disease, Parkinson's disease, prion disease, and other progressive neurological diseases that develop in the aging human central nervous system. Amyloid diseases (amyloidoses) are widespread in the elderly human population, a rapidly expanding demographic in many global populations...
February 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28318232/histology-compatible-maldi-mass-spectrometry-based-imaging-of-neuronal-lipids-for-subsequent-immunofluorescent-staining
#20
Ibrahim Kaya, Wojciech Michno, Dimitri Brinet, Yasmine Iacone, Giulia Zanni, Kaj Blennow, Henrik Zetterberg, Jörg Hanrieder
Matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables acquisition of spatial distribution maps for molecular species in situ. This can provide comprehensive insights on the pathophysiology of different diseases. However, current sample preparation and MALDI-IMS acquisition methods have limitations in preserving molecular and histological tissue morphology, resulting in interfered correspondence of MALDI-IMS data with subsequently acquired immunofluorescent staining results...
March 20, 2017: Analytical Chemistry
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