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https://www.readbyqxmd.com/read/28731452/temporal-order-of-alzheimer-s-disease-related-cognitive-marker-changes-in-blsa-and-wrap-longitudinal-studies
#1
Murat Bilgel, Rebecca L Koscik, Yang An, Jerry L Prince, Susan M Resnick, Sterling C Johnson, Bruno M Jedynak
Investigation of the temporal trajectories of currently used neuropsychological tests is critical to identifying earliest changing measures on the path to dementia due to Alzheimer's disease (AD). We used the Progression Score (PS) method to characterize the temporal trajectories of measures of verbal memory, executive function, attention, processing speed, language, and mental status using data spanning normal cognition, mild cognitive impairment, and AD from 1,661 participants with a total of 7,839 visits (age at last visit 77...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731449/cerebrospinal-fluid-neurogranin-as-a-biomarker-of-neurodegenerative-diseases-a-cross-sectional-study
#2
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Robert Nisticò, Roberto Floris, Francesco Garaci, Harald Hampel
We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n = 35), FTD (n = 9), MCI (n = 41), cognitively HC (n = 23)]...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731446/effect-of-apoe-genotype-on-synaptic-proteins-in-earlier-adult-life
#3
Lindsey I Sinclair, Seth Love
BACKGROUND: Possession of APOEɛ4 is a strong risk factor for late-onset Alzheimer's disease and is associated with loss of synaptic proteins in the elderly even in the absence of Alzheimer's disease. OBJECTIVE: We hypothesized that ɛ4 allele possession in non-demented adults aged under-75 would also be associated with alterations in the levels of synaptic proteins. METHODS: We measured synaptophysin, PSD95, drebrin, SNAP-25, and septin 7 by ELISA in hippocampus and superior temporal gyrus from 103 adults aged <75 without dementia...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731445/colivelin-ameliorates-impairments-in%C3%A2-cognitive-behaviors-and-synaptic-plasticity-in-app-ps1-transgenic-mice
#4
Meina Wu, Hui Shi, Yexin He, Li Yuan, Xuesong Qu, Jun Zhang, Zhaojun Wang, Hongyan Cai, Jinshun Qi
Alzheimer's disease (AD) is the most common cause of dementia, and effective therapeutics are lacking. Colivelin (CLN), a novel, strong humanin derivative, is effective in vitro in preventing cell death induced by AD-causative genes and amyloid-β protein (Aβ) even at a low concentration. We recently demonstrated that intrahippocampal injection of CLN prevents Aβ25-35-induced deficits in spatial memory and synaptic plasticity in normal rats. Here, we further observed the effects of chronically intranasally (i...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731443/accuracy-of-clinical-diagnosis-of-dementia-with-lewy-bodies-versus-neuropathology
#5
Ragnhild E Skogseth, Tibor Hortobágyi, Hogne Soennesyn, Luiza Chwiszczuk, Dominic Ffytche, Arvid Rongve, Clive Ballard, Dag Aarsland
BACKGROUND: The first consensus criteria for dementia with Lewy bodies (DLB) published in 1996 were revised in 2005, partly because the original clinical criteria had suboptimal sensitivity. Few studies have assessed the accuracy of the 2005 criteria applied prospectively in newly diagnosed patients who have been followed longitudinally. OBJECTIVE: To explore the correlation between clinical and pathological diagnoses in patients with DLB and Parkinson's disease with dementia (PDD)...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731440/challenges-and-considerations-related-to-studying-dementia-in-african-americans
#6
Eseosa T Ighodaro, Peter T Nelson, Walter A Kukull, Frederick A Schmitt, Erin L Abner, Allison Caban-Holt, Shoshana H Bardach, Derrick C Hord, Crystal M Glover, Gregory A Jicha, Linda J Van Eldik, Alexander X Byrd, Anita Fernander
Blacks/African Americans have been reported to be ∼2-4 times more likely to develop clinical Alzheimer's disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731435/identification-of-circulating-mir-125b-as-a-potential-biomarker-of-alzheimer-s-disease-in-app-ps1-transgenic-mouse
#7
Honghai Hong, Yang Li, Baochang Su
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive decline in cognitive abilities of the affected individuals. Biological markers are essential to identify individuals at early stages of the disease for timely therapeutic intervention. Currently, pathological biomarkers are detected either through cerebrospinal fluid analysis or brain imaging, or postmortem, all of which are expensive, invasive, or time consuming. Recently, some studies have shown that circulating miR-125b, miR-181c, miR-9, miR-191-5p, miR-26b-3p, and miR-28-3p may be biomarkers of AD...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731429/severity-of-depression-impacts-imminent-conversion-from-mild-cognitive-impairment-to-alzheimer-s-disease
#8
Michaela Defrancesco, Josef Marksteiner, Georg Kemmler, Walter Wolfgang Fleischhacker, Imrich Blasko, Eberhard A Deisenhammer
BACKGROUND: Mild cognitive impairment (MCI) has been suggested to represent a prodromal stage of dementia and to confer a high risk for conversion to dementia Alzheimer's type (DAT). OBJECTIVES: In this study, we examined the predictive value of depressive symptoms and neuropsychological variables on conversion of MCI to DAT. METHODS: Neuropsychological and clinical follow-up data of 260 MCI patients seen at the Psychiatric Memory Clinic of the Medical University of Innsbruck between 2005 and 2015 were analyzed retrospectively...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731362/greater-cognitive-deficits-with-sleep-disordered-breathing-among-individuals-with-genetic-susceptibility-to-alzheimer-s-disease-the-multi-ethnic-study-of-atherosclerosis
#9
Dayna A Johnson, Jacqueline Lane, Rui Wang, Michelle Reid, Ina Djonlagic, Annette L Fitzpatrick, Stephen R Rapp, Luenda E Charles, Ruth O'Hara, Richa Saxena, Susan Redline
RATIONALE: There are conflicting findings regarding the link between sleep apnea and cognitive dysfunction. OBJECTIVE: Investigate associations between indicators of sleep-disordered breathing (SDB) and cognitive function in the Multi-Ethnic Study of Atherosclerosis and assess effect modification by the apolipoprotein ε-4 (APOE-ε4) allele. METHODS: A diverse population (N=1,752) underwent Type 2 in-home polysomnography, which included measurement of % sleep time <90% oxyhemoglobin saturation (%Sat<90%) and apnea-hypopnea index (AHI)...
July 21, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28731260/transcriptional-regulation-of-app-by-apoe-to-boldly-go-where-no-isoform-has-gone-before-apoe-app-transcription-and-ad-hypothesised-mechanisms-and-existing-knowledge-gaps
#10
REVIEW
Liying Corinne Lee, Michele Q L Goh, Edward H Koo
Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti-amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β-protein and its precursor, the amyloid precursor protein (APP) are but a part of the disease cascade. Further, risk of AD can be modulated by a number of factors, the most impactful being the ɛ4 isoform of apolipoprotein E (apoE)...
July 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28729832/the-role-of-microglia-in-retinal-neurodegeneration-alzheimer-s-disease-parkinson-and-glaucoma
#11
REVIEW
Ana I Ramirez, Rosa de Hoz, Elena Salobrar-Garcia, Juan J Salazar, Blanca Rojas, Daniel Ajoy, Inés López-Cuenca, Pilar Rojas, Alberto Triviño, José M Ramírez
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28729535/pld1-promotes-dendritic-spine-development-by-inhibiting-adam10-mediated-n-cadherin-cleavage
#12
Li-Da Luo, Gang Li, Yun Wang
Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer's disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729427/sialylated-glycosylphosphatidylinositols-suppress-the-production-of-toxic-amyloid-%C3%AE-oligomers
#13
William Nolan, Harriet McHale-Owen, Clive Bate
The production of amyloid-β (Aβ) is a key factor driving pathogenesis in Alzheimer's disease (AD). Increasing concentrations of soluble Aβ oligomers within the brain lead to synapse degeneration and the progressive dementia characteristic of AD. Since Aβ exists in both disease-relevant (toxic) and non-toxic forms, the factors that affected the release of toxic Aβ were studied in a cell model. 7PA2 cells expressing the human amyloid precursor protein released Aβ oligomers that caused synapse damage when incubated with cultured neurons...
July 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28729192/butyrylcholinesterase-knockout-reduces-fibrillar-%C3%AE-amyloid-and-conserves-18-fdg-retention-in-5xfad-mouse-model-of-alzheimer-s-disease
#14
D R DeBay, G A Reid, I R Macdonald, G Mawko, S Burrell, E Martin, C V Bowen, S Darvesh
Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia. One hallmark of the AD brain is the deposition of β-amyloid (Aβ) plaques. AD is also a state of cholinergic dysfunction and butyrylcholinesterase (BChE) associates with Aβ pathology. A transgenic mouse (5XFAD) is an aggressive amyloidosis model, producing Aβ plaques of which BChE also associates. A derived strain (5XFAD/BChE-KO), with the BChE gene knocked out, has significantly lower fibrillar Aβ than 5XFAD mice at the same age...
July 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28728105/discovery-of-imidazopyridines-containing-isoindoline-1-3-dione-framework-as-a-new-class-of-bace1-inhibitors-design-synthesis-and-sar-analysis
#15
Sara Azimi, Afsaneh Zonouzi, Omidreza Firuzi, Aida Iraji, Mina Saeedi, Mohammad Mahdavi, Najmeh Edraki
Alzheimer's disease is characterized by chronic neurodegeneration leading to dementia. The main cause of neurodegeneration is considered to be the accumulation of amyloid-β. Inhibiting BACE1 is a well-studied approach to lower the burden of amyloid-β aggregates. We designed a series of imidazopyridines-based compounds bearing phthalimide moieties as inhibitors of BACE1. The compounds 8a-o were synthesized by the Groebke-Blackburn-Bienaymé three-component reaction of heteroaromatic amidines, aldehydes and isocyanides...
June 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28726050/a-single-center-study-a%C3%AE-42-p-tau181-csf-ratio-to-discriminate-ad-from-ftd-in-clinical-setting
#16
Andrea Vergallo, Cecilia Carlesi, Cristina Pagni, Filippo Sean Giorgi, Filippo Baldacci, Lucia Petrozzi, Roberto Ceravolo, Gloria Tognoni, Gabriele Siciliano, Ubaldo Bonuccelli
Abnormal levels of beta amyloid (Aβ42) and tau protein concentrations in the cerebral spinal fluid (CSF) have been largely described in Alzheimer's disease (AD). Thus, CSF analysis of these biomarkers has been incorporated in recent AD diagnostic criteria, and it is increasingly performed for neurodegenerative dementia diagnostic workout in clinical setting. Nevertheless, the precise biomarkers CSF features in neurodegenerative dementia, either AD or Frontotemporal dementia (FTD), are still not fully clear today...
July 19, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28724358/quality-of-care-and-quality-of-life-of-people-with-dementia-living-at-green-care-farms-a-cross-sectional-study
#17
Bram de Boer, Jan P H Hamers, Sandra M G Zwakhalen, Frans E S Tan, Hilde Verbeek
BACKGROUND: Many countries are introducing smaller, more home-like care facilities that represent a radically new approach to nursing home care for people with dementia. The green care farm is a new type of nursing home developed in the Netherlands. The goal of this study was to compare quality of care, quality of life and related outcomes in green care farms, regular small-scale living facilities and traditional nursing homes for people with dementia. METHODS: A cross-sectional design was used...
July 19, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28723964/development-of-the-korean-adult-reading-test-kart-to-estimate-premorbid-intelligence-in-dementia-patients
#18
Dahyun Yi, Eun Hyun Seo, Ji Young Han, Bo Kyung Sohn, Min Soo Byun, Jun Ho Lee, Young Min Choe, Suzy Ahn, Jong Inn Woo, Jongho Jun, Dong Young Lee
We aimed to develop a word-reading test for Korean-speaking adults using irregularly pronounced words that would be useful for estimation of premorbid intelligence. A linguist who specialized in Korean phonology selected 94 words that have irregular relationship between orthography and phonology. Sixty cognitively normal elderly (CN) and 31 patients with Alzheimer's disease (AD) were asked to read out loud the words and were administered the Wechsler Adult Intelligence Scale, 4th edition, Korean version (K-WAIS-IV)...
2017: PloS One
https://www.readbyqxmd.com/read/28723664/detecting-the-genetic-link-between-alzheimer-s-disease-and-obesity-using-bioinformatics-analysis-of-gwas-data
#19
Qi-Shuai Zhuang, Hao Zheng, Xiao-Dan Gu, Liang Shen, Hong-Fang Ji
Alzheimer's disease (AD) represents the major form of dementia in the elderly. In recent years, accumulating evidence indicate that obesity may act as a risk factor for AD, while the genetic link between the two conditions remains unclear. This bioinformatics analysis aimed to detect the genetic link between AD and obesity on single nucleotide polymorphisms (SNPs), gene, and pathway levels based on genome-wide association studies data. A total of 31 SNPs were found to be shared by AD and obesity, which were linked to 7 genes...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28720718/phosphorylation-of-amyloid-precursor-protein-by-mutant-lrrk2-promotes-aicd-activity-and-neurotoxicity-in-parkinson-s-disease
#20
Zhong-Can Chen, Wei Zhang, Ling-Ling Chua, Chou Chai, Rong Li, Lin Lin, Zhen Cao, Dario C Angeles, Lawrence W Stanton, Jian-He Peng, Zhi-Dong Zhou, Kah-Leong Lim, Li Zeng, Eng-King Tan
Mutations in LRRK2, which encodes leucine-rich repeat kinase 2, are the most common genetic cause of familial and sporadic Parkinson's disease (PD), a degenerative disease of the central nervous system that causes impaired motor function and, in advanced stages, dementia. Dementia is a common symptom of another neurodegenerative disease, Alzheimer's disease, and research suggests that there may be pathophysiological and genetic links between the two diseases. Aggregates of β amyloid [a protein produced through cleavage of amyloid precursor protein (APP)] are seen in both diseases and in PD patients carrying G2019S-mutant LRRK2...
July 18, 2017: Science Signaling
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