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https://www.readbyqxmd.com/read/28103298/perinatal-choline-supplementation-reduces-amyloidosis-and-increases-choline-acetyltransferase-expression-in-the-hippocampus-of-the-appsweps1de9-alzheimer-s-disease-model-mice
#1
Tiffany J Mellott, Olivia M Huleatt, Bethany N Shade, Sarah M Pender, Yi B Liu, Barbara E Slack, Jan K Blusztajn
Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1...
2017: PloS One
https://www.readbyqxmd.com/read/28100745/disease-progression-dependent-effects-of-trem2-deficiency-in-a-mouse-model-of-alzheimer-s-disease
#2
Taylor R Jay, Anna M Hirsch, Margaret L Broihier, Crystal M Miller, Lee E Neilson, Richard M Ransohoff, Bruce T Lamb, Gary E Landreth
: Neuroinflammation is an important contributor to Alzheimer's disease (AD) pathogenesis, as underscored by the recent identification of immune-related genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2). Understanding TREM2 function promises to provide important insights into how neuroinflammation contributes to AD pathology. However, studies so far have produced seemingly conflicting results, with reports that amyloid pathology can be both decreased and increased in TREM2-deficient AD mouse models...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100644/multicellular-hypothesis-for-the-pathogenesis-of-alzheimer-s-disease
#3
Edward J Goetzl, Bruce L Miller
Extensive abnormal interactions among microglia, astrocytes, and neurons of the CNS have been observed in proteinopathic neurodegenerative dementias of the elderly. These multicellular interactions are initiated by insoluble tangles of phosphorylated tau protein and plaques of amyloid peptides. Most research has focused on these neurotoxic proteins, but much less is known about the pathogenic roles of the responding resident and recruited neural cells. Principal interactions among the major 3 sets of CNS cells are herein considered at several levels in relation to cellular phenotypic alterations, mechanisms of cellular communication, and extent of involvement in the pathogenesis of Alzheimer's disease and related proteinopathic dementias...
January 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28100077/effects-of-m2000-d-mannuronic-acid-on-learning-memory-retrieval-and-associated-determinants-in-a-rat-model-of-alzheimer-s-disease
#4
Somayeh Athari Nik Azm, Mohammadreza Vafa, Mohammad Sharifzadeh, Majid Safa, Anis Barati, Abbas Mirshafiey
The d-mannuronic acid (M2000) is a novel nonsteroidal anti-inflammatory drug that has immunosuppressive effects together with antioxidant property. M2000 has shown a notable efficacy in experimental models of multiple sclerosis, rheumatoid arthritis, and nephrotic syndrome. In this work, the effect of M2000 on the treatment of Alzheimer's disease (AD) was performed by Morris water maze experiment, and the immunological assessments were carried out by Western blot, apoptosis (procaspase-3, Bax/Bcl2, P53), enzymatic (superoxide dismutase [SOD]), and nonenzymatic oxidative stress (malondialdehyde [MDA]) tests...
February 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28099083/update-on-alzheimer-s-disease-therapy-and-prevention-strategies
#5
W Vallen Graham, Alessandra Bonito-Oliva, Thomas P Sakmar
Alzheimer's disease (AD) is the primary cause of age-related dementia. Effective strategies to prevent and treat AD remain elusive despite major efforts to understand its basic biology and clinical pathophysiology. Significant investments in therapeutic drug discovery programs over the past two decades have yielded some important insights but no blockbuster drugs to alter the course of disease. Because significant memory loss and cognitive decline are associated with neuron death and loss of gray matter, especially in the frontal cortex and hippocampus, some focus in drug development has shifted to early prevention of cellular pathology...
January 14, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/28098506/capsicum-annuum-var-grossum-bell-pepper-inhibits-%C3%AE-secretase-activity-and-%C3%AE-amyloid1-40-aggregation
#6
Omodesola Oluwafisayo Ogunruku, Ganiyu Oboh, Sabina Passamonti, Federica Trammer, Aline Augusti Boligon
The deposition of amyloid protein as senile plaques is the major signature of Alzheimer's disease (AD). It is produced by the sequential cleavage of the amyloid precursor protein by secretases. Moreover, peppers are noted for their antiaging and cognitive enhancing properties. Thus, in this study, the effects of polyphenol-rich extracts from bell pepper on amyloid production and aggregation in vitro were investigated. Bell pepper (ripe and unripe) was extracted with methanol-1 N HCl (1:1 v/v). Thereafter, the inhibitory potentials of the extracts on β-secretase and β-amyloid1-40 aggregation were determined...
January 18, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28097868/development-of-phenothiazine-based-theranostic-compounds-that-act-both-as-inhibitors-of-%C3%AF-amyloid-aggregation-and-imaging-probes-for-amyloid-plaques-in-alzheimer-s-disease
#7
Pascal Dao, Feifei Ye, Yan Liu, Zhiyun Du, Kun Zhang, Chang-Zhi Dong, Bernard Meunier, Huixiong Chen
Early detection of Alzheimer's disease (AD) is imperative in enabling the understanding and clinical treatment of this disorder, as well as in preventing its progression. Imaging agents specifically targeting Aβ plaques in the brain and the retina may lead to the early diagnosis of AD. Among them, near infrared fluorescent imaging has emerged as an attractive tool to noninvasively identify and monitor diseases during the preclinical and early stages. In the present study, we report the design, synthesis and evaluation of a series of new near-infrared fluorescent probes...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28096464/functional-transformation-of-c-reactive-protein-by-hydrogen-peroxide
#8
Sanjay K Singh, Avinash Thirumalai, Asmita Pathak, Donald N Ngwa, Alok Agrawal
C-reactive protein (CRP) is present at sites of inflammation including amyloid plaques, atherosclerotic lesions and arthritic joints. CRP, in its native pentameric structural conformation, binds to cells and molecules which have exposed phosphocholine (PCh) groups. CRP, in its non-native pentameric structural conformation, binds to a variety of deposited, denatured and aggregated proteins, in addition to binding to PCh-containing substances. In this study, we investigated the effects of hydrogen peroxide (H2O2), a prototypical reactive oxygen species and which is also present at sites of inflammation, on the ligand recognition function of CRP...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096459/zinc-and-copper-differentially-modulate-amyloid-precursor-protein-processing-by-%C3%AE-secretase-and-amyloid-%C3%AE-peptide-production
#9
Hermeto Gerber, Fang Wu, Mitko Dimitrov, Guillermo M Garcia Osuna, Patrick C Fraering
Recent evidence suggests involvement of biometal homeostasis in the pathological mechanisms in Alzheimer's disease (AD). For example, increased intracellular copper or zinc has been linked to a reduction in secreted levels of the AD-causing amyloid-β peptide (Aβ). However, little is known about whether these biometals modulate the generation of Aβ. In the present study, we demonstrate in both cell-free and cell-based assays that zinc and copper regulate Aβ production by distinct molecular mechanisms affecting the processing by γ-secretase of its Aβ precursor protein substrate APP-C99...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096295/does-selection-for-short-sleep-duration-explain-human-vulnerability-to-alzheimer-s-disease
#10
Randolph M Nesse, Caleb E Finch, Charles L Nunn
Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer 's disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin - a peptide hormone that increases markedly during sleep - is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD...
January 16, 2017: Evolution, Medicine, and Public Health
https://www.readbyqxmd.com/read/28094952/effect-of-an-enhanced-nose-to-brain-delivery-of-insulin-on-mild-and-progressive-memory-loss-in-the-senescence-accelerated-mouse
#11
Noriyasu Kamei, Misa Tanaka, Hayoung Choi, Nobuyuki Okada, Takamasa Ikeda, Rei Itokazu, Mariko Takeda-Morishita
Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28093855/typical-and-atypical-appearance-of-early-onset-alzheimer-s-disease-a-clinical-neuroimaging-and-neuropathological-study-symposium-fundamentals-learned-from-diversity-among-typical-and-atypical-appearances
#12
Shinobu Kawakatsu 川勝 忍, Ryota Kobayashi, Hiroshi Hayashi
The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early-onset dementia, we investigated 12 patients with early-onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia...
January 17, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28093567/beta-amyloid-sequelae-in-the-eye-a-critical-review-on-its-diagnostic-significance-and-clinical-relevance-in-alzheimer-s-disease
#13
REVIEW
T M Shah, S M Gupta, P Chatterjee, M Campbell, R N Martins
Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. There is no test for its definitive diagnosis in routine clinical practice. Although phase III clinical trials have failed, only symptomatic treatment is currently available; a possible reason for these failed trials is that intervention commenced at an advanced stage of the disease. The hallmarks of an AD brain include plaques comprising of extracellular beta-amyloid (Aβ) protein aggregates and intracellular hyperphosphorylated neurofibrillary tangles of tau...
January 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28093241/new-isatin-derivative-inhibits-neurodegeneration-by-restoring-insulin-signaling-in-brain
#14
Meha Fatima Aftab, Shabbir Khan Afridi, Uzma Rasool Mughal, Aneela Karim, Darakhshan Jabeen Haleem, Nurul Kabir, Khalid M Khan, Rahman M Hafizur, Rizwana S Waraich
Diabetes is associated with neurodegeneration. Glycation ensues in diabetes and glycated proteins cause insulin resistance in brain resulting in amyloid plaques and NFTs. Also glycation enhances gliosis by promoting neuroinflammation. Currently there is no therapy available to target neurodegenration in brain therefore, development of new therapy that offers neuroprotection is critical. The objective of this study was to evaluate mechanistic effect of isatin derivative URM-II-81, an anti-glycation agent for improvement of insulin action in brain and inhibition of neurodegenration...
January 13, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28088900/synaptic-plasticity-dementia-and-alzheimer-disease
#15
Pietro Giusti, Stephen D Skaper, Laura Facci, Morena Zusso
Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment...
January 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28078981/resilience-to-alzheimer-s-disease-the-role-of-physical-activity
#16
Pedrinolla Anna, Schena Federico, Venturelli Massimo
BACKGROUND: Although Alzheimer's disease (AD) is a neurodegenerative pathology characterized by accumulation of β-amyloid plaques and neurofibrillary tangles at cerebral level, recent studies highlighted that AD might be the result of many altered physiological processes occurring at whole-organism level. The ability to adapt to stressors by "bending" but not "breaking" can be considered as "resilience". Individuals incline to withstand such pathophysiological challenges, can be considered more resilient than those that do not...
January 11, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28073379/tau-passive-immunization-inhibits-not-only-tau-but-also-a%C3%AE-pathology
#17
Chun-Ling Dai, Yunn Chyn Tung, Fei Liu, Cheng-Xin Gong, Khalid Iqbal
BACKGROUND: Accumulation of hyperphosphorylated tau protein is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Currently, there is no effective treatment available for these progressive neurodegenerative diseases. In recent years, tau immunotherapy has shown great potential in animal models. We report the effect of immunization with tau antibodies 43D against tau 6-18 and 77E9 against tau 184-195 on tau and amyloid-β (Aβ) pathologies and cognition in triple-transgenic (3×Tg)-AD mice at mild to moderate stages of the disease...
January 10, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28072821/maysin-and-its-flavonoid-derivative-from-centipedegrass-attenuates-amyloid-plaques-by-inducting-humoral-immune-response-with-th2-skewed-cytokine-response-in-the-tg-appswe-ps1de9-alzheimer-s-mouse-model
#18
Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Hyoung-Woo Bai, Seung Sik Lee, SungBeom Lee, Byung Yeoup Chung, Jae-Hyeon Cho
Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models...
2017: PloS One
https://www.readbyqxmd.com/read/28070672/opposing-effects-of-progranulin-deficiency-on-amyloid-and-tau-pathologies-via-microglial-tyrobp-network
#19
Hideyuki Takahashi, Zoe A Klein, Sarah M Bhagat, Adam C Kaufman, Mikhail A Kostylev, Tsuneya Ikezu, Stephen M Strittmatter
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies...
January 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28065262/analyzing-amyloid-%C3%AE-peptide-modulation-profiles-and-binding-sites-of-%C3%AE-secretase-modulators
#20
J Trambauer, A Fukumori, B Kretner, H Steiner
γ-Secretase is a key player in the pathogenesis of Alzheimer's disease (AD). The intramembrane-cleaving enzyme initially cleaves a C-terminal fragment of the amyloid precursor protein (APP) at the ɛ-site within its transmembrane domain to release the APP intracellular domain. Subsequent stepwise carboxy-terminal trimming cleavages eventually release amyloid-β (Aβ) peptides of 37-43 amino acids into the extracellular space. Aβ42 as well as the much less abundant Aβ43 species are highly aggregation prone and can deposit as plaques in the brains of affected patients, which are widely believed to be causative of AD...
2017: Methods in Enzymology
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