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https://www.readbyqxmd.com/read/28431180/collagenosis-of-the-deep-medullary-veins-an-underrecognized-pathologic-correlate-of-white-matter-hyperintensities-and-periventricular-infarction
#1
Julia Keith, Fu-Qiang Gao, Raza Noor, Alex Kiss, Gayathiri Balasubramaniam, Kelvin Au, Ekaterina Rogaeva, Mario Masellis, Sandra E Black
White matter hyperintensities (WMH) are prevalent. Although arteriolar disease has been implicated in their pathogenesis, venous pathology warrants consideration. We investigated relationships of WMH with histologic venous, arteriolar and white matter abnormalities and correlated findings with premortem neuroimaging. Three regions of periventricular white matter were sampled from archived autopsy brains of 24 pathologically confirmed Alzheimer disease (AD) and 18 age-matched nonAD patients. Using trichrome staining, venous collagenosis (VC) of periventricular veins (<150 µm in diameter) was scored for severity of wall thickening and occlusion; percent stenosis by collagenosis of large caliber (>200 µm) veins (laVS) was measured...
April 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28431036/effects-of-delay-duration-on-the-wms-logical-memory-performance-of-older-adults-with-probable-alzheimer-s-disease-probable-vascular-dementia-and-normal-cognition
#2
Valencia Montgomery, Katie Harris, Anthony Stabler, Lisa H Lu
Objective: To examine how the duration of time delay between Wechsler Memory Scale (WMS) Logical Memory I and Logical Memory II (LM) affected participants' recall performance. Method: There are 46,146 total Logical Memory administrations to participants diagnosed with either Alzheimer's disease (AD), vascular dementia (VaD), or normal cognition in the National Alzheimer's Disease Coordinating Center's Uniform Data Set. Results: Only 50% of the sample was administered the standard 20-35 min of delay as specified by WMS-R and WMS-III...
May 1, 2017: Archives of Clinical Neuropsychology: the Official Journal of the National Academy of Neuropsychologists
https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#3
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430602/fluoxetine-attenuates-the-impairment-of-spatial-learning-ability-and-prevents-neuron-loss-in-middle-aged-appswe-psen1de9-double-transgenic-alzheimer-s-disease-mice
#4
Jing Ma, Yuan Gao, Lin Jiang, Feng-Lei Chao, Wei Huang, Chun-Ni Zhou, Wei Tang, Lei Zhang, Chun-Xia Huang, Yi Zhang, Yan-Min Luo, Qian Xiao, Hua-Rong Yu, Rong Jiang, Yong Tang
Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer's disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430290/frequency-and-topography-of-small-cerebrovascular-lesions-in-vascular-and-in-mixed-dementia-a-post-mortem-7-tesla-magnetic-resonance-imaging-study-with-neuropathological-correlates
#5
Jacques De Reuck, Florent Auger, Nicolas Durieux, Vincent Deramecourt, Claude-Alain Maurage, Charlotte Cordonnier, Florence Pasquier, Didier Leys, Regis Bordet
<i><b>Introduction</b>: Mixed dementia (MixD) refers to a combination of definite Alzheimer's disease (AD) and vascular encephalopathy. The existence of a "pure" type of vascular dementia (VaD) is controversial. There is a need to find magnetic resonance imaging (MRI) characteristics allowing the distinction between VaD and MixD. The present post-mortem 7.0-tesla MRI compares the frequency or severity and the topography of the small cerebrovascular lesions in brains of patients with VaD and with MixD...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28430012/zo-1-expression-is-suppressed-by-gm-csf-via-mir-96-erg-in-brain-microvascular-endothelial-cells
#6
Hu Zhang, Shuhong Zhang, Jilin Zhang, Dongxin Liu, Jiayi Wei, Wengang Fang, Weidong Zhao, Yuhua Chen, Deshu Shang
The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28429640/spinal-alterations-of-reil-insula-in-alzheimer-s-disease
#7
Foivos E Petrides, Ioannis A Mavroudis, Martha Spilioti, Fotios G Chatzinikolaou, Vasiliki G Costa, Stavros J Baloyannis
Alzheimer's disease (AD) is a progressive neurodegenerative disease that involves numerous cellular and biochemical mechanisms resulting in synaptic alterations and extensive neuronal loss. It is primarily characterized by impairment of memory, associated frequently with mood disorders. Continuous studies have shown that insula may be an important target of AD, but neuropathological alterations have not been described extensively. In the present study, we attempted to describe the morphometric and morphological changes of the spines of Reil insula in AD in comparison with normal aging using a silver impregnation technique...
January 1, 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28429629/developing-indicators-of-appropriate-and-inappropriate-end-of-life-care-in-people-with-alzheimer-s-disease-cancer-or-chronic-obstructive-pulmonary-disease-for-population-level-administrative-databases-a-rand-ucla-appropriateness-study
#8
Robrecht De Schreye, Dirk Houttekier, Luc Deliens, Joachim Cohen
BACKGROUND: A substantial amount of aggressive life-prolonging treatments in the final stages of life has been reported for people with progressive life-shortening conditions. Monitoring appropriate and inappropriate end-of-life care is an important public health challenge and requires validated quality indicators. AIM: To develop indicators of appropriate and inappropriate end-of-life care for people with cancer, chronic obstructive pulmonary disease or Alzheimer's disease, measurable with population-level administrative data...
April 1, 2017: Palliative Medicine
https://www.readbyqxmd.com/read/28429562/predictors-of-the-health-related-quality-of-life-of-chinese-people-with-major-neurocognitive-disorders-and-their-caregivers-the-roles-of-self-esteem-and-caregiver-s-burden
#9
Daniel Kim-Wan Young, Petrus Yat-Nam Ng, Timothy Kwok
AIM: The present research study aimed to identify and compare the clinical and non-clinical factors that predict the self-reported and proxy-reported health-related quality of life (HRQoL) of people with major neurocognitive disorder (PwND) who are living at home in a Chinese society. METHODS: A total of 57 Chinese PwND-family caregiver dyads that were using the services of local senior centers were recruited through a cross-sectional survey with convenience sampling...
April 20, 2017: Geriatrics & Gerontology International
https://www.readbyqxmd.com/read/28429536/%C3%AE-mangostin-decreases-%C3%AE-amyloid-peptides-production-via-modulation-of-amyloidogenic-pathway
#10
Lan-Xue Zhao, Yan Wang, Ting Liu, Yan-Xia Wang, Hong-Zhuan Chen, Jian-Rong Xu, Yu Qiu
AIMS: β-amyloid (Aβ) aggregation and deposition play a central role in the pathogenic process of Alzheimer's disease (AD). α-Mangostin (α-M), a polyphenolic xanthone, have been shown to dissociate Aβ oligomers. In this study, we further investigated the effect of α-M on Aβ production and its molecular mechanism. METHODS: The Aβ and soluble amyloid precursor protein α (sAPPα) in culture medium of cortical neurons were measured by ELISA. The activities of α-, β-, and γ-secretases were assayed, and the interaction between α-M and β- or γ-secretases was simulated by molecular docking...
April 21, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28429406/haplodeficiency-of-cathepsin-d-does-not-affect-cerebral-amyloidosis-and-autophagy-in-app-ps1-transgenic-mice
#11
Shaowu Cheng, Willayat Y Wani, David A Hottman, Angela Jeong, Dongfeng Cao, Kyle J LeBlanc, Paul Saftig, Jianhua Zhang, Ling Li
Autophagy and lysosomal function are important for protein homeostasis and their dysfunction have been associated with Alzheimer's disease (AD). Increased immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are evident in amyloid plaques and neurons in patients with AD. The current study tests the hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts cerebral β-amyloidosis in APPsw/PS1dE9 (APP/PS1) double transgenic mice. Despite a significant 38% decrease of Cat D level in APP/PS1/Ctsd+/- compared to APP/PS1/Ctsd+/+ mice, no changes in steady state levels and deposition of Aβ were found in the brain...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28429235/regulation-of-human-brain-microvascular-endothelial-cell-adhesion-and-barrier-functions-by-memantine
#12
Fei Wang, Zhirong Zou, Yi Gong, Dong Yuan, Xun Chen, Tao Sun
Vascular risk factors have been linked to cognitive decline and dementia in the elderly. Microvascular inflammation, especially of the endothelium, may contribute to the progression of neurodegenerative events in Alzheimer's disease (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is a licensed drug used for the treatment of moderate to severe AD. However, little information is available regarding its anti-inflammatory effects on the endothelium. In this study, we investigated the effects of memantine on human brain microvascular endothelial dysfunction induced by the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α)...
April 20, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28429084/rs4878104-contributes-to-alzheimer-s-disease-risk-and-regulates-dapk1-gene-expression
#13
Yang Hu, Liang Cheng, Ying Zhang, Weiyang Bai, Wenyang Zhou, Tao Wang, Zhifa Han, Jian Zong, Shuilin Jin, Jun Zhang, Qinghua Jiang, Guiyou Liu
In 2006, a candidate gene study reported death-associated protein kinase 1 (DAPK1) rs4878104 variant to be significantly associated with Alzheimer's disease (AD) risk. However, the following studies showed inconsistent association results. Here, we conducted an updated analysis to investigate the potential association between rs4878104 and AD using a total of 60,751 samples (20,161 AD cases and 40,590 controls). In the pooled population, the results based on the allele and genotype genetic models show that rs4878104 variant is not significantly associated with AD risk...
April 20, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28428742/a-set-based-mixed-effect-model-for-gene-environment-interaction-and-its-application-to-neuroimaging-phenotypes
#14
Changqing Wang, Jianping Sun, Bryan Guillaume, Tian Ge, Derrek P Hibar, Celia M T Greenwood, Anqi Qiu
Imaging genetics is an emerging field for the investigation of neuro-mechanisms linked to genetic variation. Although imaging genetics has recently shown great promise in understanding biological mechanisms for brain development and psychiatric disorders, studying the link between genetic variants and neuroimaging phenotypes remains statistically challenging due to the high-dimensionality of both genetic and neuroimaging data. This becomes even more challenging when studying gene-environment interaction (G×E) on neuroimaging phenotypes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28428740/protein-quality-control-by-molecular-chaperones-in-neurodegeneration
#15
REVIEW
Aaron Ciechanover, Yong Tae Kwon
Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cannot dilute toxic substances by division, and, thus, are highly sensitive to misfolded proteins, especially as they age...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28428554/network-assisted-analysis-of-gwas-data-identifies-a-functionally-relevant-gene-module-for-childhood-onset-asthma
#16
Y Liu, M Brossard, C Sarnowski, A Vaysse, M Moffatt, P Margaritte-Jeannin, F Llinares-López, M H Dizier, M Lathrop, W Cookson, E Bouzigon, F Demenais
The number of genetic factors associated with asthma remains limited. To identify new genes with an undetected individual effect but collectively influencing asthma risk, we conducted a network-assisted analysis that integrates outcomes of genome-wide association studies (GWAS) and protein-protein interaction networks. We used two GWAS datasets, each consisting of the results of a meta-analysis of nine childhood-onset asthma GWASs (5,924 and 6,043 subjects, respectively). We developed a novel method to compute gene-level P-values (fastCGP), and proposed a parallel dense-module search and cross-selection strategy to identify an asthma-associated gene module...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428473/technical-considerations-on-scanning-and-image-analysis-for-amyloid-pet-in-dementia
#17
Go Akamatsu, Akihito Ohnishi, Kazuki Aita, Yasuhiko Ikari, Yasuji Yamamoto, Michio Senda
Brain imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), can provide essential and objective information for the early and differential diagnosis of dementia. Amyloid PET is especially useful to evaluate the amyloid-β pathological process as a biomarker of Alzheimer's disease. This article reviews critical points about technical considerations on the scanning and image analysis methods for amyloid PET...
2017: Nihon Hoshasen Gijutsu Gakkai Zasshi
https://www.readbyqxmd.com/read/28428346/sugar-and-artificially-sweetened-beverages-and-the-risks-of-incident-stroke-and-dementia-a-prospective-cohort-study
#18
Matthew P Pase, Jayandra J Himali, Alexa S Beiser, Hugo J Aparicio, Claudia L Satizabal, Ramachandran S Vasan, Sudha Seshadri, Paul F Jacques
BACKGROUND AND PURPOSE: Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially sweetened beverage consumption was associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort. METHODS: We studied 2888 participants aged >45 years for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged >60 years for incident dementia (mean age 69 [SD, 6] years; 46% men)...
April 20, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28428194/detrimental-effects-of-centrally-administered-angiotensin-ii-are-enhanced-in-a-mouse-model-of-alzheimer-disease-independently-of%C3%A2-blood-pressure
#19
Koki Takane, Yu Hasegawa, Bowen Lin, Nobutaka Koibuchi, Cheng Cao, Takashi Yokoo, Shokei Kim-Mitsuyama
BACKGROUND: The significance of brain angiotensin II in Alzheimer disease (AD) is unclear. METHODS AND RESULTS: To examine the role of brain angiotensin II in AD, intracerebroventricular angiotensin II infusion was performed on 5XFAD mice, a mouse model of AD, and wild-type mice, and the detrimental effects of brain angiotensin II was compared between the 2 strains of mice. Intracerebroventricular angiotensin II infusion significantly impaired cognitive function in 5XFAD mice but not in wild-type mice...
April 20, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28428015/plasma-neurofilament-light-chain-levels-in-alzheimer-s-disease
#20
Wenjun Zhou, Jie Zhang, Fanlong Ye, Guangzheng Xu, Hang Su, Yindan Su, Xiangyang Zhang
Plasma neurofilament light (NFL) levels may be a marker of neuronal injury. We examined whether plasma NFL might be a potential biomarker for the prodromal and dementia stages of AD. Participants included 193 cognitively normal (CN), 198 amnestic mild cognitive impairment (aMCI) and 187 Alzheimer's disease (AD) individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Plasma NFL levels were examined by the Single Molecule array (Simoa) technique. Our results showed significantly increased plasma NFL levels in both AD (50...
April 17, 2017: Neuroscience Letters
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