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https://www.readbyqxmd.com/read/29332049/free-heme-and-amyloid-%C3%AE-a-fatal-liaison-in-alzheimer-s-disease
#1
Elisabeth Chiziane, Henriette Telemann, Martin Krueger, Juliane Adler, Jürgen Arnhold, A Alia, Jörg Flemmig
While the etiology of Alzheimer's disease (AD) is still unknown, an increased formation of amyloid-β (Aβ) peptide and oxidative processes are major pathological mechanism of the disease. The interaction of Aβ with free heme leads to the formation of peroxidase-active Aβ-heme complexes. However, enzyme-kinetic data and systematic mutational studies are still missing. These aspects were addressed in this study to evaluate the role of Aβ-heme complexes in AD. The enzyme-kinetic measurements showed peroxidase-specific pH- and H2O2-dependencies...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332046/a-novel-antibody-targeting-tau-phosphorylated-at-serine-235-detects-neurofibrillary-tangles
#2
David Brici, Jürgen Götz, Rebecca M Nisbet
Alzheimer's disease is characterized by two main pathological hallmarks in the human brain: the extracellular deposition of amyloid-β as plaques and the intracellular accumulation of the hyperphosphorylated protein tau as neurofibrillary tangles (NFTs). Phosphorylated tau (p-tau) specific-antibodies and silver staining have been used to reveal three morphological stages of NFT formation: pre-NFTs, intraneuronal NFTs (iNFTs), and extraneuronal NFTs (eNFTs). Here we characterize a novel monoclonal antibody, RN235, which is specific for tau phosphorylated at serine 235, and detects iNFTs and eNFTs in brain tissue, suggesting that phosphorylation at this site is indicative of late stage changes in tau...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332042/protective-effects-of-indian-spice-curcumin-against-amyloid-%C3%AE-in-alzheimer-s-disease
#3
P Hemachandra Reddy, Maria Manczak, Xiangling Yin, Mary Catherine Grady, Andrew Mitchell, Sahil Tonk, Chandra Sekhar Kuruva, Jasvinder Singh Bhatti, Ramesh Kandimalla, Murali Vijayan, Subodh Kumar, Rui Wang, Jangampalli Adi Pradeepkiran, Gilbert Ogunmokun, Kavya Thamarai, Kandi Quesada, Annette Boles, Arubala P Reddy
The purpose of our article is to assess the current understanding of Indian spice, curcumin, against amyloid-β (Aβ)-induced toxicity in Alzheimer's disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes, and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332040/synthetic-fragment-of-receptor-for-advanced-glycation-end-products-prevents-memory-loss-and-protects-brain-neurons-in-olfactory-bulbectomized-mice
#4
Olga M Volpina, Alexandr N Samokhin, Dmitriy O Koroev, Inna V Nesterova, Tatyana D Volkova, Natalia I Medvinskaya, Pavel V Nekrasov, Olga G Tatarnikova, Anna V Kamynina, Samson M Balasanyants, Tamara A Voronina, Alexey M Kulikov, Natalia V Bobkova
Activation of receptor for advanced glycation end products (RAGE) plays an essential role in the development of Alzheimer's disease (AD). It is known that the soluble isoform of the receptor binds to ligands and prevents negative effects of the receptor activation. We proposed that peptide fragments from RAGE prevent negative effects of the receptor activation during AD neurodegeneration. We have synthesized peptide fragments from surface-exposed regions of RAGE. Peptides were intranasally administrated into olfactory bulbectomized (OBX) mice, which developed some characteristics similar to AD neurodegeneration...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332038/sex-influences-the-accuracy-of-subjective-memory-complaint-reporting-in-older-adults
#5
Erin E Sundermann, Emily C Edmonds, Lisa Delano-Wood, Douglas R Galasko, David P Salmon, Leah H Rubin, Mark W Bondi
Subjective memory complaints (SMC) are required when diagnosing amnestic mild cognitive impairment (aMCI), although their relationship with objective memory performance and Alzheimer's disease (AD) pathology remains unclear. We investigated whether the sex of the patient/participant moderates these associations. Participants were 940 normal control (NC) and aMCI participants from the Alzheimer's Disease Neuroimaging Initiative. SMC were assessed via the memory scale of the Everyday Cognition questionnaire. Discrepancy scores were calculated between self- and informant-reports and categorized into "overestimates," "comparable estimates", and "underestimates" of SMC...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332037/increased-vulnerability-of-the-hippocampus-in-transgenic-mice-overexpressing-app-and-triple-repeat-tau
#6
Andrew Arner, Edward Rockenstein, Michael Mante, Jazmin Florio, Deborah Masliah, Bahar Salehi, Anthony Adame, Cassia Overk, Eliezer Masliah, Robert A Rissman
 Alzheimer's disease (AD) is the most common tauopathy, characterized by progressive accumulation of amyloid-β (Aβ) and hyperphosphorylated tau. While pathology associated with the 4-repeat (4R) tau isoform is more abundant in corticobasal degeneration and progressive supranuclear palsy, both 3R and 4R tau isoforms accumulate in AD. Many studies have investigated interactions between Aβ and 4R tau in double transgenic mice, but few, if any, have examined the effects of Aβ with 3R tau. To examine this relationship, we crossed our APP751 mutant line with our recently characterized 3R tau mutant model to create a bigenic line (hAPP-3RTau) to model AD neuropathology...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29331877/cerebral-changes-and-disrupted-gray-matter-cortical-networks-in-asymptomatic-older-adults-at-risk-for-alzheimer-s-disease
#7
Jose L Cantero, Mercedes Atienza, Pascual Sanchez-Juan, Eloy Rodriguez-Rodriguez, Jose Luis Vazquez-Higuera, Ana Pozueta, Andrea Gonzalez-Suarez, Eduard Vilaplana, Jordi Pegueroles, Victor Montal, Rafael Blesa, Daniel Alcolea, Alberto Lleo, Juan Fortea
The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established in Alzheimer's disease, but our current knowledge about how abnormal CSF levels affect cerebral integrity, at local and network levels, is incomplete in asymptomatic older adults. Here, we have collected CSF samples and performed structural magnetic resonance imaging scans in cognitively normal elderly as part of a cross-sectional multicenter study (SIGNAL project). To identify group differences in cortical thickness, white matter volume, and properties of structural networks, participants were split into controls (N = 20), positive amyloid-β (Aβ1-42+) (N = 19), and positive phosphorylated tau (N = 18)...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29331876/app-go-protein-g%C3%AE-%C3%AE-complex-signaling-mediates-a%C3%AE-degeneration-and-cognitive-impairment-in-alzheimer-s-disease-models
#8
Elena Anahi Bignante, Nicolás Eric Ponce, Florencia Heredia, Juliana Musso, María C Krawczyk, Julieta Millán, Gustavo F Pigino, Nibaldo C Inestrosa, Mariano M Boccia, Alfredo Lorenzo
Deposition of amyloid-β (Aβ), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism of Aβ-induced degeneration in AD remains on debate. Here, we analyzed the interaction of APP with heterotrimeric Go protein in primary hippocampal cultures and found that Aβ deposition dramatically enhanced APP-Go protein interaction in dystrophic neurites. APP overexpression rendered neurons vulnerable to Aβ toxicity by a mechanism that required Go-Gβγ complex signaling and p38-mitogen-activated protein kinase activation...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29331631/the-edinburgh-ct-and-genetic-diagnostic-criteria-for-lobar-intracerebral-haemorrhage-associated-with-cerebral-amyloid-angiopathy-model-development-and-diagnostic-test-accuracy-study
#9
Mark A Rodrigues, Neshika Samarasekera, Christine Lerpiniere, Catherine Humphreys, Mark O McCarron, Philip M White, James A R Nicoll, Cathie L M Sudlow, Charlotte Cordonnier, Joanna M Wardlaw, Colin Smith, Rustam Al-Shahi Salman
BACKGROUND: Identification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype. METHODS: We identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort...
January 10, 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29331531/profiles-of-%C3%AE-amyloid-peptides-and-key-secretases-in-brain-autopsy-samples-differ-with-sex-and-apoe-%C3%AE%C2%B54-status-impact-for-risk-and-progression-of-alzheimer-disease
#10
Jennifer N K Nyarko, Maa O Quartey, Paul R Pennington, Ryan M Heistad, Doris Dea, Judes Poirier, Glen B Baker, Darrell D Mousseau
The APOE ε 4 allele was originally reported to contribute to risk of Alzheimer disease (AD) in women, yet male and female AD patient-derived data are routinely pooled. Histopathological hallmarks of AD include neurofibrillary tangles centered on hyperphosphorylated Tau and plaques composed of the β -amyloid (A β) peptide that is derived by sequential secretase-mediated cleavage of the Amyloid Protein Precursor (APP). We chose to examine profiles of A β (1-40), A β (1-42), and N-truncated (i.e. p3-related) fragments in the plaque-associated fraction of autopsied cortical and corresponding hippocampal samples from donors with a diagnosis of early-onset (EOAD) and late-onset (LOAD) AD...
January 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/29331212/prion-protein-as-a-toxic-acceptor-of-amyloid-%C3%AE-oligomers
#11
REVIEW
Silvia A Purro, Andrew J Nicoll, John Collinge
The initial report that cellular prion protein (PrPC) mediates toxicity of amyloid-β species linked to Alzheimer's disease was initially treated with scepticism, but growing evidence supports this claim. That there is a high-affinity interaction is now clear, and its molecular basis is being unraveled, while recent studies have identified possible downstream toxic mechanisms. Determination of the clinical significance of such interactions between PrPC and disease-associated amyloid-β species will require experimental medicine studies in humans...
February 15, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29331207/cerebral-amyloid-angiopathy-related-inflammation-a-case-report-presenting-diagnostic-difficulties
#12
Cecylia Rajczewska-Oleszkiewicz, Agnieszka Cyganek, Anna Stadnik, Dorota Dziewulska
We describe an 86-year-old woman with a history of hypertension who presented sudden disturbances of consciousness and left hemiparesis. Brain magnetic resonance imaging (MRI) revealed diffused hyperintensive changes on T2-weighted images localized subcortically in the white matter of both cerebral hemispheres, corresponding to acute vasogenic edema, causing moderate mass effect. Posterior reversible encephalopathy syndrome was initially diagnosed. After implementation of anti-edema intravenous steroid treatment and hypotensive therapy the symptoms began to retire, till the total regression...
January 6, 2018: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29330472/amyloid-deposition-in-a-mouse-model-humanized-at-the-transthyretin-and-retinol-binding-protein-4-loci
#13
Xiangshun Li, Yanyi Lyu, Jingling Shen, Yanshuang Mu, Lixia Qiang, Li Liu, Kimi Araki, Bruno P Imbimbo, Ken-Ichi Yamamura, Shoude Jin, Zhenghua Li
Familial amyloidotic polyneuropathy is an autosomal dominant disorder caused by a point mutation in the transthyretin (TTR) gene. The process of TTR amyloidogenesis begins with rate-limiting dissociation of the TTR tetramer. Thus, the TTR stabilizers, such as Tafamidis and Diflunisal, are now in clinical trials. Mouse models will be useful to testing the efficacy of these drugs. Although several mouse models have been generated, they all express mouse Rbp4. Thus, human TTR associates with mouse RBP4, resulting in different kinetic and thermodynamic stability profiles of TTR tetramers...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29330470/%C3%AE-ecdysterone-protects-sh-sy5y-cells-against-%C3%AE-amyloid-induced-apoptosis-via-c-jun-n-terminal-kinase-and-akt-associated-complementary-pathways
#14
Tianjiao Xu, Chengu Niu, Xiaojie Zhang, Miaoxian Dong
Recently, the significantly higher incidence of Alzheimer's disease (AD) in women than in men has been attributed to the loss of neuroprotective estrogen after menopause. Does phytoestrogen have the ability to protect against amyloid-β (Aβ) toxicity? The aim of this study was to evaluate hypothesis that β-ecdysterone (β-Ecd) protects SH-SY5Y cells from Aβ-induced apoptosis by separate signaling pathways involving protein kinase B (Akt) and c-Jun N-terminal kinase (JNK). Here, we demonstrate that phytoestrogen β-Ecd inhibits Aβ-triggered mitochondrial apoptotic pathway, as indicated by Bcl-2/Bax ratio elevation, cytochrome c (cyt c) release reduction, and caspase-9 inactivation...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29330303/mammalian-amyloidogenic-proteins-promote-prion-nucleation-in-yeast
#15
Pavithra Chandramowlishwaran, Meng Sun, Kristin L Casey, Andrey V Romanyuk, Anastasiya V Grizel, Julia V Sopova, Aleksandr A Rubel, Carmen Nussbaum-Krammer, Ina M Vorberg, Yury O Chernoff
Fibrous cross-β aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. Initial nucleation of a yeast prion by transiently overproduced prion-forming protein or its (typically, QN-rich) prion domain is efficient only in the presence of another aggregated (in most cases, QN-rich) protein. Here, we demonstrate that a fusion of the prion domain of yeast protein Sup35 to some non-QN-rich mammalian proteins, associated with amyloid diseases, promotes nucleation of Sup35 prions in the absence of preexisting aggregates...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29330300/real-time-imaging-of-yeast-cells-reveals-several-distinct-mechanisms-of-curing-of-the-ure3-prion
#16
Xiaohong Zhao, Jenna Lanz, Danielle Steinberg, Tyler Pease, Joseph M Ahearn, Evgeny E Bezsonov, Elena Staguhn, Evan Eisenberg, Daniel C Masison, Lois E Greene
The [URE3] yeast prion is the self-propagating amyloid form of the Ure2 protein. [URE3] is cured by overexpression of several yeast proteins, including Ydj1, Btn2, Cur1, Hsp42, and human DnaJB6. To better understand [URE3] curing, we used real-time imaging with a yeast strain expressing a GFP-labeled full-length Ure2 construct to monitor the curing of [URE3] over time. [URE3] yeast cells exhibited numerous fluorescent foci, and expression of the GFP-labeled Ure2 affected neither mitotic stability of [URE3] nor the rate of [URE3] curing by the curing proteins...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29330223/the-anti-oxidant-xanthorrhizol-prevents-amyloid-%C3%AE-induced-oxidative-modification-and-inactivation-of-neprilysin
#17
Chol Seung Lim, Jung-Soo Han
Activity of neprilysin (NEP), the major protease which cleaves β-amyloid (Aβ), is reportedly reduced in the brains of patients with Alzheimer's disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxy nonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess anti-oxidant and anti-inflammatory properties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced oxidative modification of NEP protein...
January 12, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29330135/apbb2-is-associated-with-amphetamine-use-and-plasma-beta-amyloids-in-patients-receiving-methadone-maintenance-treatment
#18
Chia-Chen Liu, Chiu-Ping Fang, Tung-Hsia Liu, Hsiang-Wei Kuo, Shu Chi Liu, Sheng-Chang Wang, Andrew C H Chen, Yu-Li Liu
APBB2, amyloid beta (A4) precursor protein-binding family B member 2, has been reported to be associated with opioid dependence. In this study, we reported the first time that the genetic variants in the APBB2 gene were associated with use of amphetamine in opioid dependent patients undergoing methadone maintenance treatment (MMT). 344 heroin-dependent patients undergoing MMT were recruited and assessed for use of amphetamine and opioids by urine toxicology, withdrawal severity, and side effects. DNAs were genome-widely genotyped for all patients...
January 9, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29330058/haptoglobin-and-serum-amyloid-a-as-putative-biomarker-candidates-of-naturally-occurring-bovine-respiratory-disease-in-dairy-calves
#19
Vivek Joshi, V K Gupta, A G Bhanuprakash, R S K Mandal, U Dimri, Y Ajith
Bovine respiratory disease (BRD) is one of the leading causes of morbidity and mortality in dairy calves. Identification of reliable biomarkers of naturally occurring BRD is essential for ensuring early diagnosis and treatment of calves and monitoring treatment efficacy. This need is punctuated, especially in mild to moderate cases that would greatly help to decrease recurrence and the overall prevalence of BRD. The present study was conducted to investigate the changes in serum concentrations of haptoglobin (Hpt) and serum amyloid A (SAA) and association between oxidative stress and acute phase proteins (APPs) in BRD...
January 9, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29329714/mutation-burden-profile-in-familial-alzheimer-s-disease-cases-from-india
#20
Adhikarla Syama, Somdatta Sen, Lakshmi Narayanan Kota, Biju Viswanath, Meera Purushottam, Mathew Varghese, Sanjeev Jain, Mitradas M Panicker, Odity Mukherjee
This study attempts to identify coding risk variants in genes previously implicated in Alzheimer's disease (AD) pathways, through whole-exome sequencing of subjects (N = 17) with AD, with a positive family history of dementia (familial AD). We attempted to evaluate the mutation burden in genes encoding amyloid precursor protein metabolism and previously linked to risk of dementias. Novel variants were identified in genes involved in amyloid precursor protein metabolism such as PSEN1 (chr 14:73653575, W161C, tgg > tgT), PLAT (chr 8:42039530,G272R), and SORL1 (chr11:121414373,G601D)...
December 12, 2017: Neurobiology of Aging
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