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Journal of Alzheimer's Disease: JAD

Lilian Calderón-Garcidueñas, Partha S Mukherjee, Katharina Waniek, Max Holzer, Chih-Kai Chao, Charles Thompson, Rubén Ruiz-Ramos, Ana Calderón-Garcidueñas, Maricela Franco-Lira, Rafael Reynoso-Robles, Angélica Gónzalez-Maciel, Ingolf Lachmann
Long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above USEPA standards is associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) children exhibit subcortical pretangles in infancy and cortical tau pre-tangles, NFTs, and amyloid phases 1-2 by the 2nd decade. Given their AD continuum, we measured in 507 normal cerebrospinal fluid (CSF) samples (MMC 354, controls 153, 12.82±6.73 y), a high affinity monoclonal non-phosphorylated tau antibody (non-P-Tau), as a potential biomarker of AD and axonal damage...
November 8, 2018: Journal of Alzheimer's Disease: JAD
Jose A Soria, Branko N Huisa, Steven D Edland, Irene Litvan, Guerry M Peavy, David P Salmon, Lawrence A Hansen, Douglas R Galasko, James B Brewer, Hector M González, Robert A Rissman
Clinical, neuropsychological, and neurological procedures used to diagnose Alzheimer's disease (AD) and related dementias were largely developed and validated in well-educated, non-Latino, English-speaking populations. Sociocultural and genetic differences in Latinos might influence the accuracy of clinical diagnosis of AD and other dementias. We aim to compare the accuracy of the clinical diagnosis of AD and related dementias in Latinos with the corresponding neuropathological diagnosis. From the UCSD Alzheimer's Disease Research Center longitudinal cohort, we selected all Latino participants who had autopsy neuropathological studies from 1991 to 2017...
November 8, 2018: Journal of Alzheimer's Disease: JAD
Tenielle Porter, Samantha C Burnham, Lidija Milicic, Greg Savage, Paul Maruff, Yen Ying Lim, Qiao-Xin Li, David Ames, Colin L Masters, Stephanie Rainey-Smith, Christopher C Rowe, Olivier Salvado, David Groth, Giuseppe Verdile, Victor L Villemagne, Simon M Laws
BACKGROUND: With the exception of APOE, genetic variants associated with increased Alzheimer's disease (AD) risk are characterized by small effect sizes. Polygenic risk scores (PRS) have shown utility in predicting AD risk; however, their utility for predicting decline in cognition at preclinical stages of AD is poorly understood. OBJECTIVE: To validate associations of a 22-variant AD-risk-weighted PRS with AD risk and related biomarkers and to assess its utility to predict cognitive decline...
November 8, 2018: Journal of Alzheimer's Disease: JAD
Haowei Jiang, Suman Jayadev, Michael Lardelli, Morgan Newman
RESENILIN 1 (PSEN1) and PRESENILIN 2 (PSEN2) genes are loci for mutations causing familial Alzheimer's disease (fAD). However, the function of these genes and how they contribute to fAD pathogenesis has not been fully determined. This review provides a summary of the overlapping and independent functions of the PRESENILINS with a focus on the lesser studied PSEN2. As a core component of the γ-secretase complex, the PSEN2 protein is involved in many γ-secretase-related physiological activities, including innate immunity, Notch signaling, autophagy, and mitochondrial function...
November 8, 2018: Journal of Alzheimer's Disease: JAD
Catherine A S Deane, Ian R Brown
HSPA6 (Hsp70B') is an inducible member of the Hsp70 (HSPA) family of heat shock proteins that is present in the human genome and not found in mouse and rat. Hence it is lacking in current animal models of neurodegenerative diseases. To advance knowledge of the little studied HSPA6, differentiated human neuronal SH-SY5Y cells were treated with the proteotoxic stress-inducing agent MG132. A robust induction of HSPA6 was apparent which localized to the periphery of MG132-induced protein aggregates in the neuronal cytoplasm...
November 8, 2018: Journal of Alzheimer's Disease: JAD
Hanlin Zhang, Kang Chen, Naili Wang, Di Zhang, Qian Yang, Qing Zhang, Pan Liu, Mengyao Wan, Changlin Gong, Xinyu Hong, Wenying Qiu, Xiaojing Qian, Yongmei Chen, Chao Ma
The Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS/PUMC) Human Brain Bank was established in December 2012 and had accomplished 197 brain donations by November 2017. The brain bank was based on a large-scale willed body donation program in CAMS/PUMC starting from 1999. Demographic and medical characteristic analysis of brain donors was conducted to facilitate the construction of the brain bank. The average postmortem delay of brain donors was 17.7 h and 77.7% of these donors died less than 15 km away from the brain bank...
November 5, 2018: Journal of Alzheimer's Disease: JAD
Gamze Tuna, Görsev G Yener, Gülgün Oktay, G Hüray İşlekel, F Güldal Kİrkalİ
Matrix metalloproteinases (MMPs) are substantial regulators of learning and memory and might be involved in neurodegeneration. It is known that MMPs are involved in pathogenesis of Alzheimer's disease (AD) and are particularly involved in the amyloid-β processing pathway. However, information on circulating levels of these proteins and their tissue inhibitors (TIMPs) in AD and other neurodegenerative dementia (ND) diseases such as dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) is not clear...
November 5, 2018: Journal of Alzheimer's Disease: JAD
Gina M Peloso, Alexa S Beiser, Anita L Destefano, Sudha Seshadri
Epidemiological and genetic studies have pointed to the role of cholesterol in Alzheimer's disease (AD). We explored the interaction of a genetic risk score (GRS) of AD risk alleles with mid-life plasma lipid levels (LDL-C, HDL-C, and triglycerides) on risk for AD in the Framingham Heart Study (FHS). Mid-life (between the ages of 40-60 years old) lipid levels were obtained from individuals in the FHS Original and Offspring cohorts (157 cases and 2,882 controls) with genetic data and AD status available. Cox proportional hazards regression was performed to test the interaction between mid-life lipid levels and an AD GRS, as well as the individual contributing SNPs, on risk of incident AD adjusting for age, sex, and cohort...
November 5, 2018: Journal of Alzheimer's Disease: JAD
Ibtisam Bagallab, Jorge Mauricio Reyes-Ruiz, Khalid Abulnaja, Etimad Huwait, Charles Glabe
The monoclonal antibodies 6E10 and 4G8 are among the first anti-amyloid monoclonal antibodies against Aβ and the most widely used antibodies in Alzheimer's disease research. Although the epitopes for 6E10 and 4G8 have been reported to correspond to residues 1-16 and 17-24, a more recent high-resolution mapping approach indicates that 6E10 maps to residues 4-10 while 4G8 maps to residues 18-23. To characterize the binding specificity of both antibodies in greater detail, we used immunoselection of random sequences from phage display library followed by deep sequencing and analysis of resulting patterns from thousands of immunoselected sequences...
November 5, 2018: Journal of Alzheimer's Disease: JAD
Ilaria Bacigalupo, Flavia Mayer, Eleonora Lacorte, Alessandra Di Pucchio, Fabrizio Marzolini, Marco Canevelli, Teresa Di Fiandra, Nicola Vanacore
BACKGROUND: Dementia, including Alzheimer's disease (AD), is one of the most burdensome medical conditions. Usually, the reviews that aim at calculating the prevalence of dementia include estimates from studies without assessing their methodological quality. Alzheimer's Disease International (ADI) proposed a score to assess the methodological quality of population-based studies aimed at estimating the prevalence of dementia. During the last three years, the European Commission has funded three projects (Eurodem, EuroCoDe, and ALCOVE) in order to estimate the prevalence of dementia in Europe...
November 5, 2018: Journal of Alzheimer's Disease: JAD
Ning Tang, Kasper P Kepp
Missense mutations in presenilin 1 cause early onset familial Alzheimer's disease in a way that is not understood. Increased Aβ42/Aβ40 ratios are the most consistent biochemical phenotype of such mutations in cultured cells and in vivo, and are thus considered central to the amyloid hypothesis. Previously, an inverse relation has been observed between the Aβ42/Aβ40 ratio of such mutants and the clinical age of symptom onset in patients carrying the mutation. However, a recent extensive study by Sun et al...
November 3, 2018: Journal of Alzheimer's Disease: JAD
Angel Piriz, Dolly Reyes, Atul Narkhede, Vanessa A Guzman, Fawad Viqar, Irene B Meier, Mariana Budge, Pedro Mena, Stephen Dashnaw, Joseph Lee, Christiane Reitz, Jose Gutierrez, Luis Campos, Martin Medrano, Rafael Lantigua, Richard Mayeux, Adam M Brickman
The incidence and prevalence of Alzheimer's disease (AD) dementia are higher among Caribbean Hispanics than among non-Hispanic Whites. The causes of this health disparity remain elusive, partially because of the relative limited capacity for biomedical research in the developing countries that comprise Caribbean Latin America. To begin to address this issue, we were awarded a Development Research Award from the US NIH and Fogarty International Center in order to establish the local capacity to integrate magnetic resonance imaging (MRI) into studies of cognitive aging and dementia in Dominican Republic, establish collaborations with Dominican investigators, and conduct a pilot study on the role of cerebrovascular markers in the clinical expression of AD...
November 3, 2018: Journal of Alzheimer's Disease: JAD
Zhihui Lu, Tamara B Harris, Eric J Shiroma, Jason Leung, Timothy Kwok
BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia, and mild cognitive impairment (MCI) is a transitional phase between healthy cognition and dementia. Physical activity (PA) has protective effects on cognitive decline. However, few studies have examined how PA and sedentary behavior is structured throughout the day in older adults across varied cognitive status in Hong Kong. OBJECTIVE: This study aimed to compare patterns of PA and sedentary behavior among individuals with AD, MCI, or normal cognition living in Hong Kong...
November 3, 2018: Journal of Alzheimer's Disease: JAD
Susanne Angermann, Johannes Schier, Marcus Baumann, Dominik Steubl, Christine Hauser, Georg Lorenz, Roman Günthner, Matthias C Braunisch, Stephan Kemmner, Robin Satanovskij, Bernhard Haller, Uwe Heemann, Timo Grimmer, Thomas Lehnert, Richard Bieber, Martin Pachmann, Jürgen Braun, Julia Scherf, Gabriele Schätzle, Michael Fischereder, Timo Grimmer, Christoph Schmaderer
BACKGROUND: The prevalence of cognitive impairment in hemodialysis patients is notably high. In previous studises performed in the general population, cognitive impairment has been associated with increased mortality. OBJECTIVE: We evaluated the relationship between global cognitive function tested by a short screening instrument and mortality in hemodialysis patients. METHODS: Cognitive testing was performed in 242 maintenance hemodialysis patients under standardized conditions at baseline using the Montreal Cognitive Assessment (MoCA)...
November 3, 2018: Journal of Alzheimer's Disease: JAD
Pedro Cisternas, Juan M Zolezzi, Carolina Lindsay, Daniela S Rivera, Alexis Martinez, Francisco Bozinovic, Nibaldo C Inestrosa
Alzheimer's disease (AD) is the most common cause of dementia worldwide. Despite advances in our understanding of the molecular milieu driving AD pathophysiology, no effective therapy is currently available. Moreover, various clinical trials have continued to fail, suggesting that our approach to AD must be revised. Accordingly, the development and validation of new models are highly desirable. Over the last decade, we have been working with Octodon degus (degu), a Chilean rodent, which spontaneously develops AD-like neuropathology, including increased amyloid-β (Aβ) aggregates, tau hyperphosphorylation, and postsynaptic dysfunction...
November 3, 2018: Journal of Alzheimer's Disease: JAD
Willem S Eikelboom, Jeroen G J van Rooij, Esther van den Berg, Michiel Coesmans, Lize C Jiskoot, Ellen Singleton, Rik Ossenkoppele, John C van Swieten, Harro Seelaar, Janne M Papma
Neuropsychiatric symptoms (NPS) are increasingly recognized as a core element of Alzheimer's disease (AD); however, clinicians still consider AD primarily as a cognitive disorder. We describe a case in which the under-recognition of NPS as part of AD resulted in substantial delay of an AD diagnosis, a wrong psychiatric diagnosis, and the organization of inappropriate care. The aim of this paper is to acknowledge NPS as an (early) manifestation of AD and to suggest features that may point toward underlying AD in older adults with late-life behavioral changes...
November 3, 2018: Journal of Alzheimer's Disease: JAD
H Robert Brashear, Nzeera Ketter, Jennifer Bogert, Jianing Di, Stephen P Salloway, Reisa Sperling
BACKGROUND: Amyloid-related imaging abnormalities with effusion or edema (ARIA-E) reported in patients with mild-to-moderate Alzheimer's disease in bapineuzumab phase III studies. OBJECTIVES: Assess symptoms, clinical severity, and ARIA-E outcomes, and to evaluate effects on cognition and function. METHODS: A centralized systematic sequential locked procedure and scoring system for assessment of magnetic resonance imaging scans in 1,331 APOE ɛ4 noncarriers and 1,121 carriers was conducted by experienced and trained pairs of neuroradiologists...
November 3, 2018: Journal of Alzheimer's Disease: JAD
Rebecca Palm, Christian G G Sorg, Armin Ströbel, Debby L Gerritsen, Bernhard Holle
BACKGROUND: The phenomena of severe agitation is not well understood and often not adequately treated. OBJECTIVE: This article determines the prevalence and associated factors of severe agitation in nursing home residents with dementia. METHODS: Secondary data analysis within an observational study in German nursing homes with n = 1,967 participants. We assessed severity of agitation with the Neuropsychiatric Inventory Questionnaire (NPI-Q) and defined the construct of agitation as a composite score of the NPI-Q items agitation/aggression, disinhibition, and irritability/lability; the dependent variable of severe agitation was considered as being present in residents who scored 'severe' in at least one of these symptoms...
November 3, 2018: Journal of Alzheimer's Disease: JAD
John C Gant, Inga Kadish, Kuey-Chu Chen, Olivier Thibault, Eric M Blalock, Nada M Porter, Philip W Landfield
Aging is the leading risk factor for idiopathic Alzheimer's disease (AD), indicating that normal aging processes promote AD and likely are present in the neurons in which AD pathogenesis originates. In AD, neurofibrillary tangles (NFTs) appear first in entorhinal cortex, implying that aging processes in entorhinal neurons promote NFT pathogenesis. Using electrophysiology and immunohistochemistry, we find pronounced aging-related Ca2 + dysregulation in rat entorhinal neurons homologous with the human neurons in which NFTs originate...
November 3, 2018: Journal of Alzheimer's Disease: JAD
Sarah J Banks, Xiaowei Zhuang, Ece Bayram, Chris Bird, Dietmar Cordes, Jessica Z K Caldwell, Jeffrey L Cummings
Lateralization of default mode network (DMN) functioning has been shown to change with age. Similarly, lateralization of frontal lobe function has been shown to decline in age. The impact of amyloid pathology and the progression of Alzheimer's disease (AD) on resting state lateralization has not been investigated. Due to the preferential involvement of the left hemisphere in verbal tasks, there may be a benefit to higher levels of left-lateralization in the performance of verbal memory tasks. Here we compared functional lateralization of the anterior and posterior DMN between four groups of participants: amyloid negative (Aβ-) and amyloid positive (Aβ+) groups with normal cognition (NC), and Aβ+ groups with mild cognitive impairment (Aβ+MCI) or dementia (Aβ+AD)...
November 3, 2018: Journal of Alzheimer's Disease: JAD
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