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https://www.readbyqxmd.com/read/28453484/can-better-management-of-periodontal-disease-delay-the-onset-and-progression-of-alzheimer-s-disease
#1
Alice Harding, Sarita Robinson, St John Crean, Sim K Singhrao
A risk factor relationship exists between periodontal disease and Alzheimer's disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P...
April 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28453480/a-multifunctional-biocompatible-drug-candidate-is-highly-effective-in-delaying-pathological-signs-of-alzheimer-s-disease-in-5xfad-mice
#2
Hadar Segal-Gavish, Ortal Danino, Yael Barhum, Tali Ben-Zur, Ella Shai, David Varon, Daniel Offen, Bilha Fischer
BACKGROUND: Metal-ion-chelation was suggested to prevent zinc and copper ions-induced amyloid-β (Aβ) aggregation and oxidative stress, both implicated in the pathophysiology of Alzheimer's disease (AD). In a quest for biocompatible metal-ion chelators potentially useful for AD therapy, we previously tested a series of nucleoside 5'-phosphorothioate derivatives as agents for decomposition of Cu(I)/Cu(II)/Zn(II)-Aβ-aggregates, and as inhibitors of OH radicals formation in Cu(I) or Fe(II) /H2O2 solution...
April 28, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28453478/functional-reserve-experience-participating-in-instrumental-activities-of-daily-living-is-associated-with-gender-and-functional-independence-in-mild-cognitive-impairment
#3
Courtney Berezuk, Konstantine K Zakzanis, Joel Ramirez, Anthony C Ruocco, Jodi D Edwards, Brandy L Callahan, Sandra E Black
BACKGROUND: Gender differences in instrumental activities of daily living (IADLs) in mild cognitive impairment (MCI) and Alzheimer's disease may be explained by gender differences in IADL involvement. OBJECTIVE: We introduce a novel theoretical construct, termed functional reserve, and empirically examine gender differences in IADL experience as a proxy of this reserve. METHODS: We cross-sectionally examined men (n = 502) and women (n = 340) with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI)...
April 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28448247/oleuropein-isolated-from-fraxinus-rhynchophylla-inhibits-glutamate-induced-neuronal-cell-death-by-attenuating-mitochondrial-dysfunction
#4
Mi Hye Kim, Ju-Sik Min, Joon Yeop Lee, Unbin Chae, Eun-Ju Yang, Kyung-Sik Song, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells...
April 27, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28442538/peripheral-tumor-necrosis-factor-alpha-tnf-%C3%AE-modulates-amyloid-pathology-by-regulating-blood-derived-immune-cells-and-glial-response-in-the-brain-of-ad-tnf-transgenic-mice
#5
Evi Paouri, Ourania Tzara, Georgia-Ioanna Kartalou, Sofia Zenelak, Spiros Georgopoulos
Increasing evidence has suggested that systemic inflammation along with local brain inflammation can play a significant role in Alzheimer's disease (AD) pathogenesis. Identifying key molecules that regulate the crosstalk between the immune and the central nervous system can provide potential therapeutic targets. TNF-α is a pro-inflammatory cytokine implicated in the pathogenesis of systemic inflammatory and neurodegenerative diseases such as rheumatoid arthritis (RA) and AD. Recent studies have reported that anti-TNF-α therapy or RA itself can modulate AD pathology, although the underlying mechanism is unclear...
April 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28442216/trem2-microglia-and-neurodegenerative-diseases
#6
REVIEW
Felix L Yeh, David V Hansen, Morgan Sheng
Alzheimer's disease (AD) is the most common form of dementia and the 6th leading cause of death in the US. The neuropathological hallmarks of the disease are extracellular amyloid-β (Aβ) plaques and intraneuronal hyperphosphorylated tau aggregates. Genetic variants of TREM2 (triggering receptor expressed on myeloid cells 2), a cell-surface receptor expressed selectively in myeloid cells, greatly increase the risk of AD, implicating microglia and the innate immune system as pivotal factors in AD pathogenesis...
April 22, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28441965/evaluation-of-a-dna-a%C3%AE-42-vaccine-in-adult-rhesus-monkeys-macaca-mulatta-antibody-kinetics-and-immune-profile-after-intradermal-immunization-with-full-length-dna-a%C3%AE-42-trimer
#7
Doris Lambracht-Washington, Min Fu, Pat Frost, Roger N Rosenberg
BACKGROUND: Aggregated amyloid-β peptide 1-42 (Aβ42), derived from the cellular amyloid precursor protein, is one of the pathological hallmarks of Alzheimer's disease (AD). Although active immunization against Aβ42 peptide was successful in AD mouse models and led to removal of plaques and improved memory, a similar clinical trial in humans (Aβ42 peptide immunization with QS-21 adjuvant) was stopped in phase II, when 6% of the treated patients developed encephalitis. Currently ongoing passive immunizations with the injection of preformed monoclonal antibodies against different epitopes within the Aβ1-42 peptide, which do not lead to activation of the immune system, have shown some effects in slowing AD pathology...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28441058/protein-misfolding-diseases
#8
F Ulrich Hartl
The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer and Parkinson disease, and many other pathologies...
April 24, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28439028/bgp-15-prevents-the-death-of-neurons-in-a-mouse-model-of-familial-dysautonomia
#9
Sarah B Ohlen, Magdalena L Russell, Michael J Brownstein, Frances Lefcort
Hereditary sensory and autonomic neuropathy type III, or familial dysautonomia [FD; Online Mendelian Inheritance in Man (OMIM) 223900], affects the development and long-term viability of neurons in the peripheral nervous system (PNS) and retina. FD is caused by a point mutation in the gene IKBKAP/ELP1 that results in a tissue-specific reduction of the IKAP/ELP1 protein, a subunit of the Elongator complex. Hallmarks of the disease include vasomotor and cardiovascular instability and diminished pain and temperature sensation caused by reductions in sensory and autonomic neurons...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28436391/prediction-of-conversion-to-alzheimer-s-disease-with-longitudinal-measures-and-time-to-event-data
#10
Kan Li, Wenyaw Chan, Rachelle S Doody, Joseph Quinn, Sheng Luo
BACKGROUND: Identifying predictors of conversion to Alzheimer's disease (AD) is critically important for AD prevention and targeted treatment. OBJECTIVE: To compare various clinical and biomarker trajectories for tracking progression and predicting conversion from amnestic mild cognitive impairment to probable AD. METHODS: Participants were from the ADNI-1 study. We assessed the ability of 33 longitudinal biomarkers to predict time to AD conversion, accounting for demographic and genetic factors...
April 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28435853/preclinical-alzheimer-s-disease-and-longitudinal-driving-decline
#11
Catherine M Roe, Ganesh M Babulal, Denise M Head, Sarah H Stout, Elizabeth K Vernon, Nupur Ghoshal, Brad Garland, Peggy P Barco, Monique M Williams, Ann Johnson, Rebecca Fierberg, M Scot Fague, Chengjie Xiong, Elizabeth Mormino, Elizabeth A Grant, David M Holtzman, Tammie L S Benzinger, Anne M Fagan, Brian R Ott, David B Carr, John C Morris
INTRODUCTION: Links between preclinical AD and driving difficulty onset would support the use of driving performance as an outcome in primary and secondary prevention trials among older adults (OAs). We examined whether AD biomarkers predicted the onset of driving difficulties among OAs. METHODS: 104 OAs (65+ years) with normal cognition took part in biomarker measurements, a road test, clinical and psychometric batteries and self-reported their driving habits. RESULTS: Higher values of CSF tau/Aβ42 and ptau181/Aβ42 ratios, but not uptake on PIB amyloid imaging (p=...
January 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28435465/hypertension-cerebrovascular-impairment-and-cognitive-decline-in-aged-a%C3%AE-pp-ps1-mice
#12
Maximilian Wiesmann, Valerio Zerbi, Diane Jansen, Dieter Lütjohann, Andor Veltien, Arend Heerschap, Amanda J Kiliaan
Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain structure and function in a 16-18 months old double transgenic AβPPswe/PS1dE9 (AβPP/PS1) mouse model for AD. These aging AβPP/PS1 mice showed an increased SBP linked to a declined regional CBF...
2017: Theranostics
https://www.readbyqxmd.com/read/28435263/neuroprotection-against-apoptosis-of-sk-n-mc-cells-using-rmp-7-and-lactoferrin-grafted-liposomes-carrying-quercetin
#13
Yung-Chih Kuo, Chien-Wei Tsao
A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the blood-brain barrier (BBB) and rescue degenerated neurons, acting as an Alzheimer's disease (AD) pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28433649/chronic-nicotine-attenuates-behavioral-and-synaptic-plasticity-impairments-in-a-streptozotocin-model-of-alzheimer-s-disease
#14
Esteves Im, Lopes-Aguiar C, Rossignoli Mt, Ruggiero Rn, Broggini Acs, Bueno-Junior Ls, Kandratavicius L, Monteiro Mr, Romcy-Pereira Rn, Leite Jp
Brain glucose metabolism is altered in sporadic Alzheimer's disease (sAD), whose pathologies are reproduced in rodents by intracerebroventricular (icv) infusion of streptozotocin (STZ) in subdiabetogenic doses. The icv-STZ model also culminates in central cholinergic dysfunctions, which in turn are known to underlie both the sAD cognitive decline, and synaptic plasticity impairments. Considering the cognitive-enhancing potential of chronic nicotine (Nic), we investigated whether it attenuates icv-STZ-induced impairments in recognition memory and synaptic plasticity in a cognition-relevant substrate: the hippocampal CA1-medial prefrontal cortex (mPFC) pathway...
April 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28432980/discovery-of-potential-inhibitor-against-human-acetylcholinesterase-a-molecular-docking-and-molecular-dynamics-investigation
#15
Surya Pratap Singh, Dwijendra Gupta
Alzheimer's disease (AD) is a progressive neurodegenerative disease of central nervous system among elderly people. Human acetylcholinesterase (hAChE), an important enzyme in neuronal signaling, is responsible for the degradation of acetylcholine which in turn prevents the post synaptic signal transmissions. hAChE has been an attractive target of drug discovery for the search of therapeutics against AD. In the recent past hAChE has become hot target for the investigation of new potential therapeutics. We performed virtual screening of entire database against hAChE...
April 12, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28432138/inhibition-of-drp1-ameliorates-synaptic-depression-a%C3%AE-deposition-and-cognitive-impairment-in-alzheimer-s-disease-model
#16
Seung-Hyun Baek, So Jung Park, Jae In Jeong, Sung Hyun Kim, Jihoon Han, Jae Won Kyung, Sang-Ha Baik, Yuri Choi, Bo-Youn Choi, Jinsu Park, Gahee Bahn, Ji Hyun Shin, Doo Sin Jo, Joo-Yong Lee, Choon-Gon Jang, Thiruma V Arumugam, Jongpil Kim, Jeung-Whan Han, Jae-Young Koh, Dong-Hyung Cho, Dong-Gyu Jo
Excessive mitochondrial fission is a prominent early event, and contributes to mitochondrial dysfunction, synaptic failure and neuronal cell death in the progression of Alzheimer's disease (AD). However, it remains to be determined whether inhibition of excessive mitochondrial fission is beneficial in mammal models of AD. To determine whether dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fragmentation, can be a disease-modifying therapeutic target for AD, we examine the effects of Drp1 inhibitor on mitochondrial and synaptic dysfunctions induced by oligomeric β-amyloid (Aβ) in neurons, and neuropathology and cognitive functions in APP/PS1 double transgenic AD mice...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28431735/characterization-of-an-amyloid-only-transgenic-b6c3-tg-appswe-psen1de9-85dbo-mmjax-mouse-model-of-alzheimer-s-disease
#17
G S Finnie, R Gunnarsson, J Manavis, P C Blumbergs, K A Mander, S Edwards, C Van den Heuvel, J W Finnie
The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 μm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months...
April 18, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28431620/role-of-inflammatory-molecules-in-the-alzheimer-s-disease-progression-and-diagnosis
#18
REVIEW
Eva Bagyinszky, Vo Van Giau, Kyuhwan Shim, Kyoungho Suk, Seong Soo A An, SangYun Kim
Alzheimer's disease (AD) is a complex disorder and the most common form of neurodegenerative dementia. Several genetic, environmental, and physiological factors, including inflammations and metabolic influences, are involved in the progression of AD. Inflammations are composed of complicated networks of many chemokines and cytokines with diverse cells. Inflammatory molecules are needed for the protection against pathogens, and maintaining their balances is important for normal physiological function. Recent studies demonstrated that inflammation may be involved in neurodegenerative dementia...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#19
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430602/fluoxetine-attenuates-the-impairment-of-spatial-learning-ability-and-prevents-neuron-loss-in-middle-aged-appswe-psen1de9-double-transgenic-alzheimer-s-disease-mice
#20
Jing Ma, Yuan Gao, Lin Jiang, Feng-Lei Chao, Wei Huang, Chun-Ni Zhou, Wei Tang, Lei Zhang, Chun-Xia Huang, Yi Zhang, Yan-Min Luo, Qian Xiao, Hua-Rong Yu, Rong Jiang, Yong Tang
Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer's disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice...
February 16, 2017: Oncotarget
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