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Alzheimer's Research & Therapy

Isabelle Bos, Stephanie Vos, Rik Vandenberghe, Philip Scheltens, Sebastiaan Engelborghs, Giovanni Frisoni, José Luis Molinuevo, Anders Wallin, Alberto Lleó, Julius Popp, Pablo Martinez-Lage, Alison Baird, Richard Dobson, Cristina Legido-Quigley, Kristel Sleegers, Christine Van Broeckhoven, Lars Bertram, Mara Ten Kate, Frederik Barkhof, Henrik Zetterberg, Simon Lovestone, Johannes Streffer, Pieter Jelle Visser
BACKGROUND: There is an urgent need for novel, noninvasive biomarkers to diagnose Alzheimer's disease (AD) in the predementia stages and to predict the rate of decline. Therefore, we set up the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. In this report we describe the design of the study, the methods used and the characteristics of the participants. METHODS: Participants were selected from existing prospective multicenter and single-center European studies...
July 6, 2018: Alzheimer's Research & Therapy
Saima Hilal, Frank J Wolters, Marcel M Verbeek, Hugo Vanderstichele, M Kamran Ikram, Erik Stoops, M Arfan Ikram, Meike W Vernooij
BACKGROUND: Plasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia. However, it remains underexplored whether plasma Aβ levels including the novel Aβ peptide 1-38 (Aβ1-38 ) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of plasma Aβ1-38 , Aβ1-40 , and Aβ1-42 levels with imaging markers of neurodegeneration and risk of dementia in a prospective population-based study...
June 30, 2018: Alzheimer's Research & Therapy
Tessa van Middelaar, Marieke P Hoevenaar-Blom, Willem A van Gool, Eric P Moll van Charante, Jan-Willem van Dalen, Kay Deckers, Sebastian Köhler, Edo Richard
BACKGROUND: Selecting high-risk participants for dementia prevention trials based on a modifiable dementia risk score may be advantageous, as it increases the opportunity for intervention. We studied whether a multi-domain intervention can prevent all-cause dementia and cognitive decline in older people across three different levels of a modifiable dementia risk score. METHODS: Prevention of Dementia by Intensive Vascular Care (preDIVA) is a randomised controlled trial studying the effect of multi-domain vascular care during 6-8 years on incident all-cause dementia in community-dwelling people aged 70-78 years...
June 30, 2018: Alzheimer's Research & Therapy
John E Harrison
BACKGROUND: The FDA have recently published draft guidance for the development of treatments for early Alzheimer's disease. Key features of this guidance are the advocacy of sensitive cognitive measures and a taxonomy of disease severity. Whilst desirable patterns of cognitive-functional improvement are included, specific measures, and the magnitude of required effects, are not described. MAIN SECTION: We describe key elements of the guidance content, especially with regard targeting key cognitive domains and the means by which they might be efficiently indexed in the disease stages included in the guidance...
June 29, 2018: Alzheimer's Research & Therapy
D M Vargas, M A De Bastiani, E R Zimmer, F Klamt
BACKGROUND: Alzheimer's disease (AD) is a multifactorial and complex neuropathology that involves impairment of many intricate molecular mechanisms. Despite recent advances, AD pathophysiological characterization remains incomplete, which hampers the development of effective treatments. In fact, currently, there are no effective pharmacological treatments for AD. Integrative strategies such as transcription regulatory network and master regulator analyses exemplify promising new approaches to study complex diseases and may help in the identification of potential pharmacological targets...
June 23, 2018: Alzheimer's Research & Therapy
Milos D Ikonomovic, Enrico R Fantoni, Gill Farrar, Stephen Salloway
BACKGROUND: The performance of [18 F]flutemetamol amyloid PET against histopathological standards of truth was the subject of our recent article in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring (2017;9:25-34). MAIN BODY: This viewpoint article addresses infrequently observed discordance between visual [18 F]flutemetamol PET image readings and histopathology based solely on neuritic plaque assessment by CERAD criteria, which is resolved by assessing both neuritic and diffuse plaques and/or brain atrophy...
June 23, 2018: Alzheimer's Research & Therapy
Ananya Chakraborty, Madhurima Chatterjee, Harry Twaalfhoven, Marta Del Campo Milan, Charlotte E Teunissen, Philip Scheltens, Ruud D Fontijn, Wiesje M van Der Flier, Helga E de Vries
BACKGROUND: Increasing evidence suggests that cerebral vascular dysfunction is associated with the early stages of Alzheimer's disease (AD). Vascular endothelial growth factor (VEGF) is one of the key players involved in the development and maintenance of the vasculature. Here, we hypothesized that VEGF levels in cerebrospinal fluid (CSF) may be altered in AD patients with vascular involvement, characterized by the presence of microbleeds (MB), and in vascular dementia (VaD) patients compared to controls...
June 23, 2018: Alzheimer's Research & Therapy
Gaël Chételat, Antoine Lutz, Eider Arenaza-Urquijo, Fabienne Collette, Olga Klimecki, Natalie Marchant
Psycho-affective states or traits such as stress, depression, anxiety and neuroticism are known to affect sleep, cognition and mental health and well-being in aging populations and to be associated with increased risk for Alzheimer's disease (AD). Mental training for stress reduction and emotional and attentional regulation through meditation practice might help reduce these adverse factors. So far, studies on the impact of meditation practice on brain and cognition in aging are scarce and have limitations but the findings are encouraging, showing a positive effect of meditation training on cognition, especially on attention and memory, and on brain structure and function especially in frontal and limbic structures and insula...
June 22, 2018: Alzheimer's Research & Therapy
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
Upon publication of this article [1], it was noticed that there were some inconsistencies in Tables 1, 2 and 3. Some of the superscript letters were incorrectly assigned. Please see below the correct tables.
June 20, 2018: Alzheimer's Research & Therapy
Mei Ji, Xi-Xiu Xie, Dong-Qun Liu, Xiao-Lin Yu, Yue Zhang, Ling-Xiao Zhang, Shao-Wei Wang, Ya-Ru Huang, Rui-Tian Liu
BACKGROUND: Truncated mis-disordered tau protein plays an important role in the pathogenesis of Alzheimer's disease (AD) and frontotemporal dementia (FTD). Tau294-305 , an epitope in the truncated tau, is essential for pathological tau-tau interaction and aggregation. A tau294-305 -targeted approach may have beneficial effects in the treatment of AD and FTD. METHODS: In this study, we genetically fused tau294-305 epitope to the hepatitis B virus core protein (HBc) major immunodominant region (MIR) (with the resultant protein termed T294-HBc), and we subcutaneously immunized a Tau...
June 19, 2018: Alzheimer's Research & Therapy
Krystal Herline, Frances Prelli, Pankaj Mehta, Claire MacMurray, Fernando Goñi, Thomas Wisniewski
BACKGROUND: Alzheimer's disease (AD) is characterized by physiologically endogenous proteins amyloid beta (Aβ) and tau undergoing a conformational change and accumulating as soluble oligomers and insoluble aggregates. Tau and Aβ soluble oligomers, which contain extensive β-sheet secondary structure, are thought to be the most toxic forms. The objective of this study was to determine the ability of TWF9, an anti-β-sheet conformation antibody (aβComAb), to selectively recognize pathological Aβ and phosphorylated tau in AD human tissue compared with cognitively normal age-matched controls and to improve the performance of old 3xTg-AD mice with advanced pathology in behavioral testing after acute treatment with TWF9...
June 18, 2018: Alzheimer's Research & Therapy
Prashanthi Vemuri
BACKGROUND: As human longevity increases and Alzheimer's disease (AD) increasingly becomes a significant societal burden, finding pathways or protective factors that facilitate exceptional brain aging without AD pathophysiologies (ADP) will be critical. The goal of this viewpoint is two-fold: 1) to present evidence for "exceptional brain aging" without ADP; and 2) to bring together ideas and observations from the literature and present them as testable hypotheses for biomarker studies to discover protective factors for "exceptional brain aging" without ADP and AD dementia...
June 1, 2018: Alzheimer's Research & Therapy
Madhurima Chatterjee, Marta Del Campo, Tjado H J Morrema, Matthijs de Waal, Wiesje M van der Flier, Jeroen J M Hoozemans, Charlotte E Teunissen
BACKGROUND: Synaptic and axonal loss are two major mechanisms underlying Alzheimer's disease (AD) pathogenesis, and biomarkers reflecting changes in these cellular processes are needed for early diagnosis and monitoring the progression of AD. Contactin-2 is a synaptic and axonal membrane protein that interacts with proteins involved in the pathology of AD such as amyloid precursor protein (APP) and beta-secretase 1 (BACE1). We hypothesized that AD might be characterized by changes in contactin-2 levels in the cerebrospinal fluid (CSF) and brain tissue...
June 1, 2018: Alzheimer's Research & Therapy
Venexia M Walker, Neil M Davies, Patrick G Kehoe, Richard M Martin
BACKGROUND: Drugs for dementia have been available in England since 1997. Since their launch, there have been several changes to national guidelines and initiatives that may have influenced prescribing. These include changes in National Institute for Health and Care Excellence (NICE) guidance, several government dementia strategies, the addition of dementia to the Quality and Outcomes Framework (QOF), and the expiry of drug patents. Despite this, there has been little research into the effect of these events on prescribing...
May 29, 2018: Alzheimer's Research & Therapy
David Bartrés-Faz, Gabriele Cattaneo, Javier Solana, Josep M Tormos, Alvaro Pascual-Leone
BACKGROUND: The contribution of psychological factors to brain health and resilience remains poorly investigated. Furthermore, their possible interaction with 'classical' cognitive reserve (CR) estimates in predicting perceived mental health and cognitive status has not been specifically addressed. METHODS: We obtained data from 1081 adults responding to questionnaires on the three meaning in life (MiL) dimensions: purpose in life (PiL), sense of coherence (SoC), and engagement with life (EwL)...
May 24, 2018: Alzheimer's Research & Therapy
Giorgio G Fumagalli, Paola Basilico, Andrea Arighi, Martina Bocchetta, Katrina M Dick, David M Cash, Sophie Harding, Matteo Mercurio, Chiara Fenoglio, Anna M Pietroboni, Laura Ghezzi, John van Swieten, Barbara Borroni, Alexandre de Mendonça, Mario Masellis, Maria C Tartaglia, James B Rowe, Caroline Graff, Fabrizio Tagliavini, Giovanni B Frisoni, Robert Laforce, Elizabeth Finger, Sandro Sorbi, Elio Scarpini, Jonathan D Rohrer, Daniela Galimberti
BACKGROUND: In patients with frontotemporal dementia, it has been shown that brain atrophy occurs earliest in the anterior cingulate, insula and frontal lobes. We used visual rating scales to investigate whether identifying atrophy in these areas may be helpful in distinguishing symptomatic patients carrying different causal mutations in the microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame (C9ORF72) genes. We also analysed asymptomatic carriers to see whether it was possible to visually identify brain atrophy before the appearance of symptoms...
May 24, 2018: Alzheimer's Research & Therapy
Grégory Operto, Raffaele Cacciaglia, Oriol Grau-Rivera, Carles Falcon, Anna Brugulat-Serrat, Pablo Ródenas, Rubén Ramos, Sebastián Morán, Manel Esteller, Nuria Bargalló, José Luis Molinuevo, Juan Domingo Gispert
BACKGROUND: The ε4 allele of the apolipoprotein E gene (APOE-ε4) is the strongest genetic factor for late-onset Alzheimer's disease. During middle age, cognitively healthy APOE-ε4 carriers already show several brain alterations that resemble those of Alzheimer's disease (AD), but to a subtler degree. These include microstructural white matter (WM) changes that have been proposed as one of the earliest structural events in the AD cascade. However, previous studies have focused mainly on comparison of APOE-ε4 carriers vs noncarriers...
May 24, 2018: Alzheimer's Research & Therapy
Stina Syvänen, Greta Hultqvist, Tobias Gustavsson, Astrid Gumucio, Hanna Laudon, Linda Söderberg, Martin Ingelsson, Lars Lannfelt, Dag Sehlin
BACKGROUND: Amyloid-β (Aβ) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer's disease (AD). Despite recent progress targeting aggregated forms of Aβ, low antibody brain penetrance remains a challenge. In the present study, we used transferrin receptor (TfR)-mediated transcytosis to facilitate brain uptake of our previously developed Aβ protofibril-selective mAb158, with the aim of increasing the efficacy of immunotherapy directed toward soluble Aβ protofibrils...
May 24, 2018: Alzheimer's Research & Therapy
Silvia Kyungjin Lho, Tae Hui Kim, Kyung Phil Kwak, Kayoung Kim, Bong Jo Kim, Shin Gyeom Kim, Jeong Lan Kim, Tae Hyun Kim, Seok Woo Moon, Jae Young Park, Joon Hyuk Park, Seonjeong Byun, Seung Wan Suh, Ji Young Seo, Yoonseop So, Seung-Ho Ryu, Jong Chul Youn, Kyoung Hwan Lee, Dong Young Lee, Dong Woo Lee, Seok Bum Lee, Jung Jae Lee, Ju Ri Lee, Hyeon Jeong, Hyun-Ghang Jeong, Jin Hyeong Jhoo, Kyuhee Han, Jong Woo Hong, Ji Won Han, Ki Woong Kim
BACKGROUND: We investigated the effects of lifetime cumulative ginseng intake on cognitive function in a community-dwelling population-based prospective cohort of Korean elders. METHODS: Community-dwelling elders (N = 6422; mean age = 70.2 ± 6.9 years, education = 8.0 ± 5.3 years, female = 56.8%) from the Korean Longitudinal Study on Cognitive Aging and Dementia were included. Among them, 3918 participants (61.0%) completed the 2-year and 4-year follow-up evaluations...
May 24, 2018: Alzheimer's Research & Therapy
Steinunn Thordardottir, Elena Rodriguez-Vieitez, Ove Almkvist, Daniel Ferreira, Laure Saint-Aubert, Anne Kinhult-Ståhlbom, Håkan Thonberg, Michael Schöll, Eric Westman, Anders Wall, Maria Eriksdotter, Henrik Zetterberg, Kaj Blennow, Agneta Nordberg, Caroline Graff
BACKGROUND: The range of onset ages within some PSEN1 families is wide, and a few cases of reduced penetrance of PSEN1 mutations have been reported. However, published data on reduced penetrance have been limited to clinical histories, often collected retrospectively and lacking biomarker information. We present a case of reduced penetrance of the PSEN1 H163Y mutation in a carrier prospectively followed for 22 years. METHODS: Two brothers (A and B), both carriers of the H163Y mutation, were followed between 1995 and 2017...
May 10, 2018: Alzheimer's Research & Therapy
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