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Alzheimer's Research & Therapy

Tingting Sha, Wenwei Cheng, Yan Yan
BACKGROUND: Substantial evidence indicates that the relationship between blood pressure (BP) measures and cognitive functioning is inconsistent, complex, and age-related. Pulse pressure (PP), which can not only reflect arterial stiffness and but also represent the chronic effects of hypertension other than BP itself, has been considered as a better predictor of cognitive impairment. However, evidence on the association of cognitive function with PP has not been investigated extensively...
March 12, 2018: Alzheimer's Research & Therapy
Nicolai Franzmeier, Julia Hartmann, Alexander N W Taylor, Miguel Á Araque-Caballero, Lee Simon-Vermot, Lana Kambeitz-Ilankovic, Katharina Bürger, Cihan Catak, Daniel Janowitz, Claudia Müller, Birgit Ertl-Wagner, Robert Stahl, Martin Dichgans, Marco Duering, Michael Ewers
BACKGROUND: Recent evidence derived from functional magnetic resonance imaging (fMRI) studies suggests that functional hubs (i.e., highly connected brain regions) are important for mental health. We found recently that global connectivity of a hub in the left frontal cortex (LFC connectivity) is associated with relatively preserved memory abilities and higher levels of protective factors (education, IQ) in normal aging and Alzheimer's disease. These results suggest that LFC connectivity supports reserve capacity, alleviating memory decline...
March 6, 2018: Alzheimer's Research & Therapy
Alan J Thomas, Fariba Mahin-Babaei, Mohammad Saidi, Debbie Lett, John Paul Taylor, Lauren Walker, Johannes Attems
BACKGROUND: Dementia due to Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the two most common neurodegenerative causes of dementia. They commonly occur together, especially in older people, but clinical identification of these diseases in dementia is difficult in such circumstances. We therefore conducted a study using cases with both comprehensive prospective clinical assessments and complete neuropathological examination to determine if it is possible to identify such mixed cases clinically and to determine features which may identify DLB in the presence of AD dementia...
March 1, 2018: Alzheimer's Research & Therapy
Shaoming Sang, Xiaoli Pan, Zhichun Chen, Fan Zeng, Shumei Pan, Huimin Liu, Lirong Jin, Guoqiang Fei, Changpeng Wang, Shuhua Ren, Fangyang Jiao, Weiqi Bao, Weiyan Zhou, Yihui Guan, Yiqiu Zhang, Hongcheng Shi, Yanjiang Wang, Xiang Yu, Yun Wang, Chunjiu Zhong
BACKGROUND: The underlying mechanism of brain glucose hypometabolism, an invariant neurodegenerative feature that tightly correlates with cognitive impairment and disease progression of Alzheimer's disease (AD), remains elusive. METHODS: Positron emission tomography with 2-[18 F]fluoro-2-deoxy-D-glucose (FDG-PET) was used to evaluate brain glucose metabolism, presented as the rate of 2-[18 F]fluoro-2-deoxy-D-glucose standardized uptake value ratio (FDG SUVR) in patients with AD or control subjects and in mice with or without thiamine deficiency induced by a thiamine-deprived diet...
March 1, 2018: Alzheimer's Research & Therapy
Frederic Brosseron, Andreas Traschütz, Catherine N Widmann, Markus P Kummer, Pawel Tacik, Francesco Santarelli, Frank Jessen, Michael T Heneka
BACKGROUND: Neuroinflammation has gained increasing attention as a potential contributing factor in Alzheimer's disease (AD) pathology. A clinical cerebrospinal fluid biomarker capable of monitoring this process during the course of the disease has yet to emerge, chiefly owing to contradictory research findings. In this study, we sought to clarify the utility of inflammatory biomarkers in diagnostic procedures of AD in three steps: (1) to screen for proteins that are robustly detectable in cerebrospinal fluid; (2) based on this analysis, to explore any associations between the analytically robust markers and salient pathological features of AD; and (3) to determine the discriminative power of these markers in the clinical diagnosis of AD...
February 26, 2018: Alzheimer's Research & Therapy
Hanneke F M Rhodius-Meester, Hilkka Liedes, Ted Koene, Afina W Lemstra, Charlotte E Teunissen, Frederik Barkhof, Philip Scheltens, Mark van Gils, Jyrki Lötjönen, Wiesje M van der Flier
BACKGROUND: Survival after dementia diagnosis varies considerably. Previous studies were focused mainly on factors related to demographics and comorbidity rather than on Alzheimer's disease (AD)-related determinants. We set out to answer the question whether markers with proven diagnostic value also have prognostic value. We aimed to identify disease-related determinants associated with mortality in patients with AD. METHODS: We included 616 patients (50% female; age 67 ± 8 years; mean Mini Mental State Examination score 22 ± 3) with dementia due to AD from the Amsterdam Dementia Cohort...
February 20, 2018: Alzheimer's Research & Therapy
Elisa Canu, Elisabetta Sarasso, Massimo Filippi, Federica Agosta
BACKGROUND: A growing number of pharmacological and nonpharmacological trials have been performed to test the efficacy of approved or experimental treatments in Alzheimer disease (AD) and mild cognitive impairment (MCI). In this context, functional magnetic resonance imaging (fMRI) may be a good candidate to detect brain changes after a short period of treatment. MAIN BODY: This critical review aimed to identify and discuss the available studies that have tested the efficacy of pharmacological and nonpharmacological treatments in AD and MCI cases using task-based or resting-state fMRI measures as primary outcomes...
February 20, 2018: Alzheimer's Research & Therapy
Fernando Bartolome, Macarena de la Cueva, Consuelo Pascual, Desiree Antequera, Tamara Fernandez, Carmen Gil, Ana Martinez, Eva Carro
BACKGROUND: The phosphodiesterase (PDE) 7 inhibitor S14 is a cell-permeable small heterocyclic molecule that is able to cross the blood-brain barrier. We previously found that intraperitoneal treatment with S14 exerted neuroprotection in an Alzheimer's disease (AD) model (in APP/PS1 mice). The objective of this study was to investigate the neurogenic and cellular effects of oral administration of S14 on amyloid β (Aβ) overload. METHODS: We orally administered the PDE7 inhibitor S14 (15 mg/kg/day) or vehicle in 6-month-old APP/PS1 mice...
February 20, 2018: Alzheimer's Research & Therapy
Jaeyoon Chung, Xiaoling Zhang, Mariet Allen, Xue Wang, Yiyi Ma, Gary Beecham, Thomas J Montine, Steven G Younkin, Dennis W Dickson, Todd E Golde, Nathan D Price, Nilüfer Ertekin-Taner, Kathryn L Lunetta, Jesse Mez, Richard Mayeux, Jonathan L Haines, Margaret A Pericak-Vance, Gerard Schellenberg, Gyungah R Jun, Lindsay A Farrer
BACKGROUND: Simultaneous consideration of two neuropathological traits related to Alzheimer's disease (AD) has not been attempted in a genome-wide association study. METHODS: We conducted genome-wide pleiotropy analyses using association summary statistics from the Beecham et al. study (PLoS Genet 10:e1004606, 2014) for AD-related neuropathological traits, including neuritic plaque (NP), neurofibrillary tangle (NFT), and cerebral amyloid angiopathy (CAA). Significant findings were further examined by expression quantitative trait locus and differentially expressed gene analyses in AD vs...
February 20, 2018: Alzheimer's Research & Therapy
Evan Mayo-Wilson, Susan Hutfless, Tianjing Li, Gillian Gresham, Nicole Fusco, Jeffrey Ehmsen, James Heyward, Swaroop Vedula, Diana Lock, Jennifer Haythornthwaite, Jennifer L Payne, Theresa Cowley, Elizabeth Tolbert, Lori Rosman, Claire Twose, Elizabeth A Stuart, Hwanhee Hong, Peter Doshi, Catalina Suarez-Cuervo, Sonal Singh, Kay Dickersin
The correct title of the article [1] should be "Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol". The article is a protocol for a methodological study, not a systematic review.
February 16, 2018: Alzheimer's Research & Therapy
Joseph P M Kane, Ajenthan Surendranathan, Allison Bentley, Sally A H Barker, John-Paul Taylor, Alan J Thomas, Louise M Allan, Richard J McNally, Peter W James, Ian G McKeith, David J Burn, John T O'Brien
BACKGROUND: The prevalence of dementia with Lewy bodies (DLB) and dementia in Parkinson's disease (PDD) in routine clinical practice is unclear. Prevalence rates observed in clinical and population-based cohorts and neuropathological studies vary greatly. Small sample sizes and methodological factors in these studies limit generalisability to clinical practice. METHODS: We investigated prevalence in a case series across nine secondary care services over an 18-month period, to determine how commonly DLB and PDD cases are diagnosed and reviewed within two regions of the UK...
February 15, 2018: Alzheimer's Research & Therapy
Maximilian Pohland, Maren Pellowska, Heike Asseburg, Stephanie Hagl, Martina Reutzel, Aljoscha Joppe, Dirk Berressem, Schamim H Eckert, Mario Wurglics, Manfred Schubert-Zsilavecz, Gunter P Eckert
BACKGROUND: Current approved drugs for Alzheimer's disease (AD) only attenuate symptoms, but do not cure the disease. The pirinixic acid derivate MH84 has been characterized as a dual gamma-secretase/proliferator activated receptor gamma (PPARγ) modulator in vitro. Pharmacokinetic studies in mice showed that MH84 is bioavailable after oral administration and reaches the brain. We recently demonstrated that MH84 improved mitochondrial dysfunction in a cellular model of AD. In the present study, we extended the pharmacological characterization of MH84 to 3-month-old Thy-1 AβPPSL mice (harboring the Swedish and London mutation in human amyloid precursor protein (APP)) which are characterized by enhanced AβPP processing and cerebral mitochondrial dysfunction, representing a mouse model of early AD...
February 13, 2018: Alzheimer's Research & Therapy
Chiung-Chih Chang, Ya-Ting Chang, Chi-Wei Huang, Shih-Jen Tsai, Shih-Wei Hsu, Shu-Hua Huang, Chen-Chang Lee, Wen-Neng Chang, Chun-Chung Lui, Chia-Yi Lien
BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disease, and genetic differences may mediate neuronal degeneration. In humans, a single-nucleotide polymorphism in the B-cell chronic lymphocytic leukemia/lymphoma-2 (Bcl-2) gene, rs956572, has been found to significantly modulate Bcl-2 protein expression in the brain. The Bcl-2 AA genotype has been associated with reduced Bcl-2 levels and lower gray matter volume in healthy populations. We hypothesized that different Bcl-2 genotype groups may modulate large-scale brain networks that determine neurobehavioral test scores...
February 8, 2018: Alzheimer's Research & Therapy
Emma Muñoz-Moreno, Raúl Tudela, Xavier López-Gil, Guadalupe Soria
BACKGROUND: Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present...
February 7, 2018: Alzheimer's Research & Therapy
Frank Jessen, Annika Spottke, Henning Boecker, Frederic Brosseron, Katharina Buerger, Cihan Catak, Klaus Fliessbach, Christiana Franke, Manuel Fuentes, Michael T Heneka, Daniel Janowitz, Ingo Kilimann, Christoph Laske, Felix Menne, Peter Nestor, Oliver Peters, Josef Priller, Verena Pross, Alfredo Ramirez, Anja Schneider, Oliver Speck, Eike Jakob Spruth, Stefan Teipel, Ruth Vukovich, Christine Westerteicher, Jens Wiltfang, Steffen Wolfsgruber, Michael Wagner, Emrah Düzel
BACKGROUND: Deep phenotyping and longitudinal assessment of predementia at-risk states of Alzheimer's disease (AD) are required to define populations and outcomes for dementia prevention trials. Subjective cognitive decline (SCD) is a pre-mild cognitive impairment (pre-MCI) at-risk state of dementia, which emerges as a highly promising target for AD prevention. METHODS: The German Center for Neurodegenerative Diseases (DZNE) is conducting the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), which focuses on the characterization of SCD in patients recruited from memory clinics...
February 7, 2018: Alzheimer's Research & Therapy
Hugo Geerts, Athan Spiros, Patrick Roberts
BACKGROUND: Despite a tremendous amount of information on the role of amyloid in Alzheimer's disease (AD), almost all clinical trials testing this hypothesis have failed to generate clinically relevant cognitive effects. METHODS: We present an advanced mechanism-based and biophysically realistic quantitative systems pharmacology computer model of an Alzheimer-type neuronal cortical network that has been calibrated with Alzheimer Disease Assessment Scale, cognitive subscale (ADAS-Cog) readouts from historical clinical trials and simulated the differential impact of amyloid-beta (Aβ40 and Aβ42) oligomers on glutamate and nicotinic neurotransmission...
February 2, 2018: Alzheimer's Research & Therapy
Chun-Ling Dai, Wen Hu, Yunn Chyn Tung, Fei Liu, Cheng-Xin Gong, Khalid Iqbal
BACKGROUND: Accumulating evidence indicates that Tau pathology can spread from neuron to neuron by intake and coaggregation of the hyperphosphorylated Tau (p-Tau) seeds with the host neuron protein. Thus, clearance of Tau seeds by immunization with Tau antibodies could provide a potential therapeutic opportunity to block the spread of the pathology in Alzheimer's disease (AD) and other tauopathies. We report prevention of the seeding and spread of tau pathology with mouse monoclonal antibody 43D against the N-terminal projection domain of Tau (Tau 6-18) in triple-transgenic AD (3 × Tg-AD) mice...
January 31, 2018: Alzheimer's Research & Therapy
Ana-María Lacosta, María Pascual-Lucas, Pedro Pesini, Diego Casabona, Virginia Pérez-Grijalba, Iván Marcos-Campos, Leticia Sarasa, Jesus Canudas, Hassnae Badi, Inmaculada Monleón, Itziar San-José, Josep Munuera, Octavio Rodríguez-Gómez, Carla Abdelnour, Asunción Lafuente, Mar Buendía, Mercè Boada, Lluis Tárraga, Agustín Ruiz, Manuel Sarasa
BACKGROUND: Immunotherapy targeting the amyloid-β (Aβ) peptide is a promising strategy for the treatment of Alzheimer's disease (AD); however, none of the active or passive vaccines tested have been demonstrated to be effective to date. We have developed the first active vaccine against the C-terminal end of Aβ40 , ABvac40, and assessed its safety and tolerability in a phase I clinical trial. METHODS: A randomised, double-blind, placebo-controlled, parallel-group, phase I study of ABvac40 was conducted with patients aged 50-85 years with mild to moderate AD...
January 29, 2018: Alzheimer's Research & Therapy
Kalicharan Patra, Antoninus Soosaipillai, Sigrid Botne Sando, Camilla Lauridsen, Guro Berge, Ina Møller, Gøril Rolfseng Grøntvedt, Geir Bråthen, Ilijana Begcevic, Simon Moussaud, Lennart Minthon, Oskar Hansson, Eleftherios P Diamandis, Linda R White, Henrietta M Nielsen
BACKGROUND: Kallikrein 6 (KLK6) is known to be an age-related protease expressed at high levels in the central nervous system. It was previously shown to be involved in proteolysis of extracellular proteins implicated in neurodegenerative diseases such as Alzheimer's disease (AD), prompting validation of KLK6 as a potential biomarker of disease. However, analyses of both plasma and cerebrospinal fluid (CSF) levels of KLK6 in patients with AD have been inconclusive. We present a detailed analysis of KLK6 in plasma and CSF in two separate cohorts in a cross-sectional and a longitudinal clinical setting...
January 29, 2018: Alzheimer's Research & Therapy
Fernando Goñi, Mitchell Martá-Ariza, Krystal Herline, Daniel Peyser, Allal Boutajangout, Pankaj Mehta, Eleanor Drummond, Frances Prelli, Thomas Wisniewski
BACKGROUND: Oligomeric forms of amyloid-β (Aβ) and tau are increasing being recognized as key toxins in the pathogenesis of Alzheimer's disease (AD). METHODS: We developed a novel monoclonal antibody (mAb), GW-23B7, that recognizes β-sheet secondary structure on pathological oligomers of neurodegenerative diseases. RESULTS: The pentameric immunoglobulin M kappa chain (IgMκp) we developed specifically distinguishes intra- and extracellular pathology in human AD brains...
January 29, 2018: Alzheimer's Research & Therapy
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