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Alzheimer's Research & Therapy

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https://www.readbyqxmd.com/read/29284531/cerebrovascular-and-amyloid-pathology-in-predementia-stages-the-relationship-with-neurodegeneration-and-cognitive-decline
#1
Isabelle Bos, Frans R Verhey, Inez H G B Ramakers, Heidi I L Jacobs, Hilkka Soininen, Yvonne Freund-Levi, Harald Hampel, Magda Tsolaki, Åsa K Wallin, Mark A van Buchem, Ania Oleksik, Marcel M Verbeek, Marcel Olde Rikkert, Wiesje M van der Flier, Philip Scheltens, Pauline Aalten, Pieter Jelle Visser, Stephanie J B Vos
BACKGROUND: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia. METHODS: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies...
December 29, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29258624/a-selenium-species-in-cerebrospinal-fluid-predicts-conversion-to-alzheimer-s-dementia-in-persons-with-mild-cognitive-impairment
#2
Marco Vinceti, Annalisa Chiari, Marcel Eichmüller, Kenneth J Rothman, Tommaso Filippini, Carlotta Malagoli, Jennifer Weuve, Manuela Tondelli, Giovanna Zamboni, Paolo F Nichelli, Bernhard Michalke
BACKGROUND: Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form. METHODS: We determined concentrations of selenium species in cerebrospinal fluid sampled at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin...
December 19, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29246250/posterior-atrophy-predicts-time-to-dementia-in-patients-with-amyloid-positive-mild-cognitive-impairment
#3
Jung-Min Pyun, Young Ho Park, Hang-Rai Kim, Jeewon Suh, Min Ju Kang, Beom Joon Kim, Young Chul Youn, Jae-Won Jang, SangYun Kim
BACKGROUND: In patients with amyloid-positive mild cognitive impairment (MCI), neurodegenerative biomarkers such as medial temporal lobe atrophy (MTA) are useful to predict disease progression to dementia. Although posterior atrophy (PA) is a well-known neurodegenerative biomarker of Alzheimer's disease, little is known about PA as a predictor in patients with amyloid-positive MCI. METHODS: We included 258 patients with amyloid-positive MCI with at least one follow-up visit, and who had low cerebrospinal fluid (CSF) β-amyloid1-42 concentration...
December 16, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29246249/oligomeric-forms-of-amyloid-%C3%AE-protein-in-plasma-as-a-potential-blood-based-biomarker-for-alzheimer-s-disease
#4
Min Jeong Wang, SangHak Yi, Jee-Young Han, So Young Park, Jae-Won Jang, In Kook Chun, Sang Eun Kim, Byoung Sub Lee, Gwang Je Kim, Ji Sun Yu, Kuntaek Lim, Sung Min Kang, Young Ho Park, Young Chul Youn, Seong Soo A An, SangYun Kim
BACKGROUND: Soluble amyloid-β (Aβ) oligomers are the major toxic substances associated with the pathology of Alzheimer's disease (AD). The ability to measure Aβ oligomer levels in the blood would provide simple and minimally invasive tools for AD diagnostics. In the present study, the recently developed Multimer Detection System (MDS) for AD, a new enzyme-linked immunosorbent assay for measuring Aβ oligomers selectively, was used to detect Aβ oligomers in the plasma of patients with AD and healthy control individuals...
December 15, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29246246/rho-gtpases-as-therapeutic-targets-in-alzheimer-s-disease
#5
REVIEW
Byron J Aguilar, Yi Zhu, Qun Lu
The progress we have made in understanding Alzheimer's disease (AD) pathogenesis has led to the identification of several novel pathways and potential therapeutic targets. Rho GTPases have been implicated as critical components in AD pathogenesis, but their various functions and interactions make understanding their complex signaling challenging to study. Recent advancements in both the field of AD and Rho GTPase drug development provide novel tools for the elucidation of Rho GTPases as a viable target for AD...
December 15, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29229003/comparative-binding-properties-of-the-tau-pet-tracers-thk5117-thk5351-pbb3-and-t807-in-postmortem-alzheimer-brains
#6
Laetitia Lemoine, Per-Göran Gillberg, Marie Svedberg, Vladimir Stepanov, Zhisheng Jia, Jinghai Huang, Sangram Nag, He Tian, Bernardino Ghetti, Nobuyuki Okamura, Makoto Higuchi, Christer Halldin, Agneta Nordberg
BACKGROUND: The aim of this study was to compare the binding properties of several tau positron emission tomography tracers-THK5117, THK5351, T807 (also known as AV1451; flortaucipir), and PBB3-head to head in the same human brain tissue. METHODS: Binding assays were performed to compare the regional distribution of 3H-THK5117 and 3H-THK5351 in postmortem tissue from three Alzheimer's disease (AD) cases and three control subjects in frontal and temporal cortices as well as in the hippocampus...
December 11, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29221491/a-phase-iii-randomized-trial-of-gantenerumab-in-prodromal-alzheimer-s-disease
#7
Susanne Ostrowitzki, Robert A Lasser, Ernest Dorflinger, Philip Scheltens, Frederik Barkhof, Tania Nikolcheva, Elizabeth Ashford, Sylvie Retout, Carsten Hofmann, Paul Delmar, Gregory Klein, Mirjana Andjelkovic, Bruno Dubois, Mercè Boada, Kaj Blennow, Luca Santarelli, Paulo Fontoura
BACKGROUND: Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-β (Aβ) and removes Aβ plaques by Fc receptor-mediated phagocytosis. In the SCarlet RoAD trial, we assessed the efficacy and safety of gantenerumab in prodromal Alzheimer's disease (AD). METHODS: In this randomized, double-blind, placebo-controlled phase III study, we investigated gantenerumab over 2 years. Patients were randomized to gantenerumab 105 mg or 225 mg or placebo every 4 weeks by subcutaneous injection...
December 8, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29212555/study-partners-should-be-required-in-preclinical-alzheimer-s-disease-trials
#8
REVIEW
Joshua D Grill, Jason Karlawish
BACKGROUND: In an effort to intervene earlier in Alzheimer's disease (AD), clinical trials are testing promising candidate therapies in preclinical disease. Preclinical AD trial participants are cognitively normal, functionally independent, and autonomous decision-makers. Yet, like AD dementia trials, preclinical trials require dual enrollment of a participant and a knowledgeable informant, or study partner. MAIN TEXT: The requirement of dyadic enrollment is a barrier to recruitment and may present unique ethical challenges...
December 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29212527/anemia-is-associated-with-incidence-of-dementia-a-national-health-screening-study-in-korea-involving-37-900-persons
#9
Su-Min Jeong, Dong Wook Shin, Ji Eun Lee, Jung Hyeon Hyeon, Jinkook Lee, SangYun Kim
BACKGROUND: The aim of this study was to investigate whether anemia is associated with dementia incidence in the elderly. METHODS: Using the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database, we identified 66-year-old subjects (n = 37,900) who were free of dementia and stroke. Anemia (hemoglobin < 12 g/dl for women and < 13 g/dl for men) and the severity of anemia (mild, moderate, or severe) were defined using World Health Organization criteria...
December 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29197423/amnestic-mci-patients-experiences-after-disclosure-of-their-amyloid-pet-result-in-a-research-context
#10
Gwendolien Vanderschaeghe, Jolien Schaeverbeke, Rose Bruffaerts, Rik Vandenberghe, Kris Dierickx
BACKGROUND: Biomarkers such as amyloid imaging are increasingly used for diagnosis in the early stages of Alzheimer's disease. Very few studies have examined this from the perspective of the patient. To date, there is only limited evidence about how patients experience and value disclosure in an early disease stage. METHODS: Semistructured interviews were carried out with 38 patients with amnestic mild cognitive impairment as part of an investigator-driven diagnostic trial (EudraCT, 2013-004671-12; registered on 20 June 2014) in which participants could opt to know the binary outcome (positive/negative) result of their amyloid positron emission tomography (PET) scan...
December 2, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29191219/neurons-derived-from-sporadic-alzheimer-s-disease-ipscs-reveal-elevated-tau-hyperphosphorylation-increased-amyloid-levels-and-gsk3b-activation
#11
Anna Ochalek, Balázs Mihalik, Hasan X Avci, Abinaya Chandrasekaran, Annamária Téglási, István Bock, Maria Lo Giudice, Zsuzsanna Táncos, Kinga Molnár, Lajos László, Jørgen E Nielsen, Bjørn Holst, Kristine Freude, Poul Hyttel, Julianna Kobolák, András Dinnyés
BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia, affecting one in eight adults over 65 years of age. The majority of AD cases are sporadic, with unknown etiology, and only 5% of all patients with AD present the familial monogenic form of the disease. In the present study, our aim was to establish an in vitro cell model based on patient-specific human neurons to study the pathomechanism of sporadic AD. METHODS: We compared neurons derived from induced pluripotent stem cell (iPSC) lines of patients with early-onset familial Alzheimer's disease (fAD), all caused by mutations in the PSEN1 gene; patients with late-onset sporadic Alzheimer's disease (sAD); and three control individuals without dementia...
December 1, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29169407/the-clinical-significance-of-plasma-clusterin-and-a%C3%AE-in-the-longitudinal-follow-up-of-patients-with-alzheimer-s-disease
#12
Jung-Lung Hsu, Wei-Ju Lee, Yi-Chu Liao, Shuu-Jiun Wang, Jong-Ling Fuh
BACKGROUND: Clusterin and beta-amyloid (Aβ) are involved in the pathogenesis of Alzheimer's disease (AD). The clinical significance of plasma clusterin and Aβ in AD progression remains controversial. METHODS: We recruited 322 patients with AD and 88 controls between August 2012 and June 2013. All participants were evaluated at baseline with a clinical assessment, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scales. Patients with AD were evaluated annually with the MMSE and Neuropsychiatric Inventory (NPI) scale during the 2-year follow-up period...
November 23, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29121998/circulating-brain-enriched-micrornas-as-novel-biomarkers-for-detection-and-differentiation-of-neurodegenerative-diseases
#13
Kira S Sheinerman, Jon B Toledo, Vladimir G Tsivinsky, David Irwin, Murray Grossman, Daniel Weintraub, Howard I Hurtig, Alice Chen-Plotkin, David A Wolk, Leo F McCluskey, Lauren B Elman, John Q Trojanowski, Samuil R Umansky
BACKGROUND: Minimally invasive specific biomarkers of neurodegenerative diseases (NDs) would facilitate patient selection and disease progression monitoring. We describe the assessment of circulating brain-enriched microRNAs as potential biomarkers for Alzheimer's disease (AD), frontotemporal dementia (FTD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). METHODS: In this case-control study, the plasma samples were collected from 250 research participants with a clinical diagnosis of AD, FTD, PD, and ALS, as well as from age- and sex-matched control subjects (n = 50 for each group), recruited from 2003 to 2015 at the University of Pennsylvania Health System, including the Alzheimer's Disease Center, the Parkinson's Disease and Movement Disorders Center, the Frontotemporal Degeneration Center, and the Amyotrophic Lateral Sclerosis Clinic...
November 9, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29096697/race-modifies-the-relationship-between-cognition-and-alzheimer-s-disease-cerebrospinal-fluid-biomarkers
#14
Jennifer C Howell, Kelly D Watts, Monica W Parker, Junjie Wu, Alexander Kollhoff, Thomas S Wingo, Cornelya D Dorbin, Deqiang Qiu, William T Hu
BACKGROUND: African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD...
November 2, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29070066/the-edinburgh-consensus-preparing-for-the-advent-of-disease-modifying-therapies-for-alzheimer-s-disease
#15
LETTER
Craig W Ritchie, Tom C Russ, Sube Banerjee, Bob Barber, Andrew Boaden, Nick C Fox, Clive Holmes, Jeremy D Isaacs, Ira Leroi, Simon Lovestone, Matt Norton, John O'Brien, Jim Pearson, Richard Perry, James Pickett, Adam D Waldman, Wai Lup Wong, Martin N Rossor, Alistair Burns
CONTEXT: This commentary discusses the implications of disease-modifying treatments for Alzheimer's disease which seem likely to appear in the next few years and results from a meeting of British experts in neurodegenerative diseases in Edinburgh. The availability of such treatments would help change public and professional attitudes and accelerate engagement with the prodromal and preclinical populations who might benefit from them. However, this would require an updated understanding of Alzheimer's disease, namely the important distinction between Alzheimer's disease and Alzheimer's dementia...
October 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29061195/preclinical-effects-of-apoe-%C3%AE%C2%B54-on-cerebrospinal-fluid-a%C3%AE-42-concentrations
#16
Ronald Lautner, Philip S Insel, Tobias Skillbäck, Bob Olsson, Mikael Landén, Giovanni B Frisoni, Sanna-Kaisa Herukka, Harald Hampel, Anders Wallin, Lennart Minthon, Oskar Hansson, Kaj Blennow, Niklas Mattsson, Henrik Zetterberg
BACKGROUND: From earlier studies it is known that the APOE ε2/ε3/ε4 polymorphism modulates the concentrations of cerebrospinal fluid (CSF) beta-amyloid1-42 (Aβ42) in patients with cognitive decline due to Alzheimer's disease (AD), as well as in cognitively healthy controls. Here, in a large cohort consisting solely of cognitively healthy individuals, we aimed to evaluate how the effect of APOE on CSF Aβ42 varies by age, to understand the association between APOE and the onset of preclinical AD...
October 23, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29041968/dynamic-changes-of-oligomeric-amyloid-%C3%AE-levels-in-plasma-induced-by-spiked-synthetic-a%C3%AE-42
#17
Seong Soo A An, Byoung-Sub Lee, Ji Sun Yu, Kuntaek Lim, Gwang Je Kim, Ryan Lee, Shinwon Kim, Sungmin Kang, Young Ho Park, Min Jeong Wang, Young Soon Yang, Young Chul Youn, SangYun Kim
BACKGROUND: A reliable blood-based assay is required to properly diagnose and monitor Alzheimer's disease (AD). Many attempts have been made to develop such a diagnostic tool by measuring amyloid-β oligomers (AβOs) in the blood, but none have been successful in terms of method reliability. We present a multimer detection system (MDS), initially developed for the detection of prion oligomers in the blood, to detect AβOs. METHODS: To characterize Aβ in the blood, plasma was spiked with synthetic amyloid-β (Aβ) and incubated over time...
October 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29017593/incremental-value-of-biomarker-combinations-to-predict-progression-of-mild-cognitive-impairment-to-alzheimer-s-dementia
#18
Lutz Frölich, Oliver Peters, Piotr Lewczuk, Oliver Gruber, Stefan J Teipel, Hermann J Gertz, Holger Jahn, Frank Jessen, Alexander Kurz, Christian Luckhaus, Michael Hüll, Johannes Pantel, Friedel M Reischies, Johannes Schröder, Michael Wagner, Otto Rienhoff, Stefanie Wolf, Chris Bauer, Johannes Schuchhardt, Isabella Heuser, Eckart Rüther, Fritz Henn, Wolfgang Maier, Jens Wiltfang, Johannes Kornhuber
BACKGROUND: The progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia can be predicted by cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers. Since most biomarkers reveal complementary information, a combination of biomarkers may increase the predictive power. We investigated which combination of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)-sum-of-boxes, the word list delayed free recall from the Consortium to Establish a Registry of Dementia (CERAD) test battery, hippocampal volume (HCV), amyloid-beta1-42 (Aβ42), amyloid-beta1-40 (Aβ40) levels, the ratio of Aβ42/Aβ40, phosphorylated tau, and total tau (t-Tau) levels in the CSF best predicted a short-term conversion from MCI to AD dementia...
October 10, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28982376/gene-suppression-approaches-to-neurodegeneration
#19
REVIEW
Rhia Ghosh, Sarah J Tabrizi
Gene suppression approaches have emerged over the last 20 years as a novel therapeutic approach for the treatment of neurodegenerative diseases. These include RNA interference and anti-sense oligonucleotides, both of which act at the post-transcriptional level, and genome-editing techniques, which aim to repair the responsible mutant gene. All serve to inhibit the expression of disease-causing proteins, leading to the potential prevention or even reversal of the disease phenotype. In this review we summarise the main developments in gene suppression strategies, using examples from Huntington's disease and other inherited causes of neurodegeneration, and explore how these might illuminate a path to tackle other proteinopathy-associated dementias in the future...
October 5, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28982375/pkr-involvement-in-alzheimer-s-disease
#20
REVIEW
Jacques Hugon, François Mouton-Liger, Julien Dumurgier, Claire Paquet
BACKGROUND: Brain lesions in Alzheimer's disease (AD) are characterized by Aβ accumulation, neurofibrillary tangles, and synaptic and neuronal vanishing. According to the amyloid cascade hypothesis, Aβ1-42 oligomers could trigger a neurotoxic cascade with kinase activation that leads to tau phosphorylation and neurodegeneration. Detrimental pathways that are associated with kinase activation could also be linked to the triggering of direct neuronal death, the production of free radicals, and neuroinflammation...
October 5, 2017: Alzheimer's Research & Therapy
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