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Micaela Mitolo, Caterina Tonon, Chiara La Morgia, Claudia Testa, Valerio Carelli, Raffaele Lodi
BACKGROUND: Bright light treatment is a therapeutic intervention mainly used to treat sleep and circadian disturbances in Alzheimer's disease (AD) patients. Recently, a handful of studies also focused on the effect on cognition and behavior. Conflicting findings are reported in the literature, and no definite conclusions have been drawn about its specific therapeutic effect. SUMMARY: The aim of this review is to provide a critical evaluation of available evidence in this field, highlighting the specific characteristics of effective bright light treatment...
December 11, 2018: Dementia and Geriatric Cognitive Disorders
Hossein Safarizadeh, Zahra Garkani-Nejad
Alzheimer's disease is characterized using amyloid-beta (Aβ) aggregation. The present work was carried out to extend and design a novel quantitative structure-activity relationship (QSAR) model on inhibition efficiency of some of new 2-arylethenylquinoline derivatives against the Aβ1-42 peptide aggregation. The QSAR study, molecular docking and molecular dynamics (MD) simulations were performed to explore the influence of the structural features and investigate the molecular mechanism of ligands interactions with the Aβ1-42 peptide...
December 4, 2018: Journal of Molecular Graphics & Modelling
Ann D Cohen, Susan M Landau, Beth E Snitz, William E Klunk, Kaj Blennow, Henrik Zetterberg
Alzheimer's disease (AD) is characterized by amyloid plaques and tau pathology (neurofibrillary tangles and neuropil threads). Amyloid plaques are primarily composed of aggregated and oligomeric β-amyloid (Aβ) peptides ending at position 42 (Aβ42). The development of fluid and PET biomarkers for Alzheimer's disease (AD), has allowed for detection of Aβ pathology in vivo and marks a major advancement in understanding the role of Aβ in Alzheimer's disease (AD). In the recent National Institute on Aging and Alzheimer's Association (NIA-AA) Research Framework, AD is defined by the underlying pathology as measured in patients during life by biomarkers (Jack et al...
December 8, 2018: Molecular and Cellular Neurosciences
Adnan Cetin, Fikret Türkan, Parham Taslimi, İlhami Gulçin
Novel substituted thiophene derivatives (1, 2a-e, 3, and 4) were synthesized and their structures were characterized by infrared radiation, nuclear magnetic resonance, and mass analysis. These novel substituted thiophene derivatives were effective inhibitor compounds of the carbonic anhydrase I and II isozymes (hCA I and II), and acetylcholinesterase (AChE) enzyme with K i values in the range of 447.28 to 1004.65 nM for hCA I, 309.44 to 935.93 nM for hCA II, and 0.28 to 4.01 nM for AChE, respectively...
December 10, 2018: Journal of Biochemical and Molecular Toxicology
Yiming Chen, Huimin Fan, Chen Xu, Wenli Hu, Bingran Yu
Alzheimer's disease (AD) is an incurable neurodegenerative brain disorder that exhibits clear pathologic changes in the hippocampus. Traditional drug delivery systems are ineffective due to the existence of the blood-brain barrier (BBB). In this study, an efficient, stable, and easily constructed nanosystem (CB-Gd-Cy5.5) based on the cholera toxin B subunit (CB) is designed to improve the efficiency of drug delivery to the brain, especially the hippocampus. Through intranasal administration, CB-Gd-Cy5.5 is easily delivered to the brain without intervention by the BBB...
December 7, 2018: Macromolecular Bioscience
Yaron Ilan
Microtubules (MT) and actin microfilaments are dynamic cytoskeleton components involved in a range of intracellular processes. MTs play a role in cell division, beating of cilia and flagella, and intracellular transport. Over the past decades, much knowledge has been gained regarding MT function and structure, and its role in underlying disease progression. This makes MT potential therapeutic targets for various disorders. Disturbances in MT and their associated proteins are the underlying cause of diseases such as Alzheimer's disease, cancer, and several genetic diseases...
December 10, 2018: Journal of Cellular Physiology
Michael S Rafii
Alzheimer's disease (AD) pathology and early-onset dementia develop almost universally in Down syndrome (DS). AD is defined neuropathologically by the presence of extracellular plaques of aggregated amyloid β protein and intracellular neurofibrillary tangles (NFTs) of aggregated hyperphosphorylated tau protein. The development of radiolabeled positron emission tomography (PET) ligands for amyloid plaques and tau tangles enables the longitudinal assessment of the spatial pattern of their accumulation in relation to symptomatology...
December 8, 2018: Developmental Neurobiology
Nadege Morisot, Anthony L Berger, Khanhky Phamluong, Alan Cross, Dorit Ron
Fyn is a member of the Src family of protein tyrosine kinases (PTKs) that plays an important role not only in normal synaptic functions but also in brain pathologies including alcohol use disorder. We previously reported that repeated cycles of binge drinking and withdrawal activate Fyn in the dorsomedial striatum (DMS) of rodents, and that Fyn signaling in the DMS contributes to rat alcohol intake and relapse. Here, we used AZD0530, a CNS penetrable inhibitor of Src PTKs developed for the treatment of Alzheimer disease and cancer and tested its efficacy to suppress alcohol-dependent molecular and behavioral effects...
December 7, 2018: Addiction Biology
Fatemeh Ahmadi-Motamayel, Mohammad Taghi Goodarzi, Shabnam Tarazi, Mehrangiz Vahabian
AIM: The aim of this study was to evaluate acetylcholinesterase (AChE) and pseudocholinesterase (PChE) in whole saliva in patients with Alzheimer's disease (AD) and in healthy subjects. Saliva has a high potential for keeping track of general health and diseases. AD is a type of dementia with reduction in brain cholinergic markers that causes memory, thinking, and behavior problems. Up to 90% decrease in AChE activity has been observed in AD. METHODS AND RESULTS: Thirty healthy subjects and 30 patients with AD participated in this study...
December 11, 2018: Special Care in Dentistry
Nathan M Stall, Sanghun J Kim, Kate A Hardacre, Prakesh S Shah, Sharon E Straus, Susan E Bronskill, Lisa M Lix, Chaim M Bell, Paula A Rochon
BACKGROUND: Most dementia care occurs in the community with support from informal caregivers who are often distressed. Dementia caregiver distress is known to be hazardous to the caregiver's health, but the impact on the dementia care recipient is not well known. METHODS: We searched the Medline, Embase, PsycINFO, CINAHL, and Cochrane databases from inception until June 2017 for studies investigating the association of informal caregiver distress with health outcomes of community-dwelling dementia care recipients...
December 10, 2018: Journal of the American Geriatrics Society
J K Kuring, J L Mathias, L Ward
There appears to be a link between depression/anxiety/PTSD and dementia, although the evidence is incomplete and the reason is unclear. Mental illness may cause dementia or may be prodromal or comorbid with dementia, or dementia may trigger a relapse of symptoms in individuals with a history of mental illness. This study examined the link between depression/anxiety/PTSD and dementia by evaluating the prevalence of these disorders in people with dementia, relative to their healthy peers. Existing meta-analyses have examined the prevalence of clinically-significant depression and anxiety in Alzheimer's disease (AD), and depression in frontotemporal dementia (FTD), but have not considered vascular dementia (VaD), dementia with Lewy bodies (DLB), PTSD, or anxiety in FTD...
December 7, 2018: Neuropsychology Review
Qing Yang, Jianan Lin, Huiyuan Zhang, Yingna Liu, Mo Kan, Zhiru Xiu, Xijun Chen, Xingcheng Lan, Xiaohua Li, Xiaozheng Shi, Na Li, Xiaobo Qu
The objective of this study was to investigate the neuroprotective and antioxidant effects of ginsenoside compound K (CK) in a model of scopolamine hydrobromide-induced, memory-impaired mice. The role of CK in the regulation of amyloid β (Aβ) and its capacity to activate the Nrf2/Keap1 signaling pathway were also studied due to their translational relevance to Alzheimer's disease. The Morris water maze was used to assess spatial memory functions. Levels of superoxide dismutase, glutathione peroxidase, and malondialdehyde in brain tissues were tested...
December 7, 2018: Journal of Molecular Neuroscience: MN
Shanna L Burke, Tianyan Hu, Mitra Naseh, Nicole M Fava, Janice O'Driscoll, Daniel Alvarez, Linda B Cottler, Ranjan Duara
OBJECTIVE: A lack of understanding of the causes of attrition in longitudinal studies of older adults may lead to higher attrition rates and bias longitudinal study results. In longitudinal epidemiological studies of Alzheimer's disease and related dementias, high rates of attrition may cause a systematic underestimation of dementia prevalence and skew the characterization of the disease. This can compromise the generalizability of the study results and any inferences based on the surviving sample may grossly misrepresent the importance of the risk factors for dementia...
December 10, 2018: Aging Clinical and Experimental Research
Tan-Zhen Xu, Xiao-Yan Shen, Ling-Ling Sun, Ya-Li Chen, Bi-Qiong Zhang, Da-Ke Huang, Wei-Zu Li
Oxidative stress and neuroinflammation are important in the pathogenesis of ageing and age‑related neurodegenerative diseases, including Alzheimer's disease. NADPH oxidase 2 (NOX2) is a major source of reactive oxygen species (ROS) in the brain. The nucleotide‑binding oligomerisation domain (NOD)‑like receptor protein 1 (NLRP1) inflammasome is responsible for the formation of pro‑inflammatory molecules in neurons. Whether the NOX2‑NLRP1 inflammasome signalling pathway is involved in neuronal ageing and age‑related damage remains to be elucidated...
November 30, 2018: International Journal of Molecular Medicine
Lu Zhao, William Matloff, Kaida Ning, Hosung Kim, Ivo D Dinov, Arthur W Toga
Brain structural morphology differs with age. This study examined age-differences in surface-based morphometric measures of cortical thickness, volume, and surface area in a well-defined sample of 8137 generally healthy UK Biobank participants aged 45-79 years. We illustrate that the complexity of age-related brain morphological differences may be related to the laminar organization and regional evolutionary history of the cortex, and age of about 60 is a break point for increasing negative associations between age and brain morphology in Alzheimer's disease (AD)-prone areas...
December 7, 2018: Cerebral Cortex
Gary Glazner, Daniel B Kaplan
No abstract text is available yet for this article.
December 11, 2018: JAMA: the Journal of the American Medical Association
X Raymond Gao, Hua Huang, Heejin Kim
The macula, located near the center of the retina in the human eye, is responsible for providing critical functions, such as central, sharp vision. Structural changes in the macula are associated with many ocular diseases, including age-related macular degeneration (AMD) and glaucoma. Although macular thickness is a highly heritable trait, there are no prior reported genome-wide association studies (GWASs) of it. Here, we describe the first GWAS of macular thickness, which was measured by spectral-domain optical coherence tomography using 68,423 participants from the UK Biobank cohort...
December 7, 2018: Human Molecular Genetics
Heidi I L Jacobs, Rachel F Buckley
No abstract text is available yet for this article.
October 1, 2018: Brain: a Journal of Neurology
Ciro De Luca, Anna Maria Colangelo, Lilia Alberghina, Michele Papa
Coagulation and the immune system interact in several physiological and pathological conditions, including tissue repair, host defense, and homeostatic maintenance. This network plays a key role in diseases of the central nervous system (CNS) by involving several cells (CNS resident cells, platelets, endothelium, and leukocytes) and molecular pathways (protease activity, complement factors, platelet granule content). Endothelial damage prompts platelet activation and the coagulation cascade as the first physiological step to support the rescue of damaged tissues, a flawed rescuing system ultimately producing neuroinflammation...
2018: Frontiers in Cellular Neuroscience
Simin Mahinrad, Marjolein Bulk, Isabelle van der Velpen, Ahmed Mahfouz, Willeke van Roon-Mom, Neal Fedarko, Sevil Yasar, Behnam Sabayan, Diana van Heemst, Louise van der Weerd
Animal studies suggest the involvement of natriuretic peptides (NP) in several brain functions that are known to be disturbed during Alzheimer's disease (AD). However, it remains unclear whether such findings extend to humans. In this study, we aimed to: (1) map the gene expression and localization of NP and their receptors (NPR) in human post-mortem brain tissue; (2) compare the relative amounts of NP and NPR between the brain tissue of AD patients and non-demented controls, and (3) compare the relative amounts of NP between the cerebrospinal fluid (CSF) of AD patients and non-demented controls...
2018: Frontiers in Neuroscience
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