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https://www.readbyqxmd.com/read/29780864/change-in-retinal-structural-anatomy-during-the-preclinical-stage-of-alzheimer-s-disease
#1
Cláudia Y Santos, Lenworth N Johnson, Stuart E Sinoff, Elena K Festa, William C Heindel, Peter J Snyder
Introduction: We conducted a 27-month longitudinal study of mid-life adults with preclinical Alzheimer's disease (AD), using spectral domain optical coherence tomography to compare changes in volume and thickness in all retinal neuronal layers to those of age-matched healthy control subjects. Methods: Fifty-six older adults (mean age = 65.36 years) with multiple risk factors for AD completed spectral domain optical coherence tomography retinal imaging and cognitive testing at baseline...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29768974/brain-phospholipid-precursors-administered-post-injury-reduce-tissue-damage-and-improve-neurological-outcome-in-experimental-traumatic-brain-injury
#2
Orli Thau-Zuchman, Rita Noutel Gomes, Simon Christopher Dyall, Meirion Davis, John V Priestley, Martine Groenendijk, Martijn DE Wilde, Jordi Lopez-Tremoleda, Adina T Michael-Titus
Traumatic brain injury (TBI) leads to cellular loss, destabilisation of membranes, disruption of synapses and altered brain connectivity, and increased risk of neurodegenerative disease. A significant and long-lasting decrease in phospholipids (PL), essential membrane constituents, has recently been reported in plasma and brain tissue, in human and experimental TBI. We hypothesised that supporting PL synthesis post-injury could improve outcome after TBI. We tested this hypothesis using a multi-nutrient combination designed to support the biosynthesis of phospholipids and available for clinical use...
May 17, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29679667/systemic-delivery-of-bace1-sirna-through-neuron-targeted-nanocomplexes-for-treatment-of-alzheimer-s-disease
#3
Pengzhen Wang, Xiaoyao Zheng, Qian Guo, Peng Yang, Xiaoying Pang, Kang Qian, Wei Lu, Qizhi Zhang, Xinguo Jiang
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme to cleave the amyloid precursor protein to develop Alzheimer's disease (AD). Reducing BACE1 expression in central neuron through RNA interference technology shows great promise to overcome AD. However, to obtain an efficient and neurons-specific delivery of siRNA against BACE1 through systemic administration remains challenging. Here, we design and prepare siRNA nano-carriers based on PEGylated poly(2-(N,N-dimethylamino) ethyl methacrylate) (PEG-PDMAEMA) modified with both the CGN peptide for blood-brain barrier (BBB) penetration and the Tet1 peptide for neuron-specific binding...
April 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29581224/vascular-cognitive-impairment-linked-to-brain-endothelium-inflammation-in-early-stages-of-heart-failure-in-mice
#4
Mateusz G Adamski, Magdalena Sternak, Tasnim Mohaissen, Dawid Kaczor, Joanna M Wierońska, Monika Malinowska, Iwona Czaban, Katarzyna Byk, Kristina S Lyngsø, Kamil Przyborowski, Pernille B L Hansen, Grzegorz Wilczyński, Stefan Chlopicki
BACKGROUND: Although advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved. METHODS AND RESULTS: Tgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte-specific overexpression of G-αq*44 protein were studied before the end-stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively...
March 26, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29571287/chronic-oxycodone-induces-axonal-degeneration-in-rat-brain
#5
Ruping Fan, Lisa M Schrott, Thomas Arnold, Stephen Snelling, Meghana Rao, Derrel Graham, Angela Cornelius, Nadejda L Korneeva
BACKGROUND: Chronic opioid therapy for non-malignant pain conditions has significantly increased over the last 15 years. Recently, the correlation between opioid analgesics and alternations in brain structure, such as leukoencephalopathy, axon demyelination, and white matter lesions, has been demonstrated in patients with a history of long-term use of prescription opioids. The exact mechanisms underlying the neurotoxic effect of opioids on the central nervous system are still not fully understood...
March 23, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29520228/lipopolysaccharide-associates-with-amyloid-plaques-neurons-and-oligodendrocytes-in-alzheimer-s-disease-brain-a-review
#6
REVIEW
Xinhua Zhan, Boryana Stamova, Frank R Sharp
This review proposes that lipopolysaccharide (LPS, found in the wall of all Gram-negative bacteria) could play a role in causing sporadic Alzheimer's disease (AD). This is based in part upon recent studies showing that: Gram-negative E. coli bacteria can form extracellular amyloid; bacterial-encoded 16S rRNA is present in all human brains with over 70% being Gram-negative bacteria; ultrastructural analyses have shown microbes in erythrocytes of AD patients; blood LPS levels in AD patients are 3-fold the levels in control; LPS combined with focal cerebral ischemia and hypoxia produced amyloid-like plaques and myelin injury in adult rat cortex...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29499767/white-matter-changes-in-alzheimer-s-disease-a-focus-on-myelin-and-oligodendrocytes
#7
REVIEW
Sara E Nasrabady, Batool Rizvi, James E Goldman, Adam M Brickman
Alzheimer's disease (AD) is conceptualized as a progressive consequence of two hallmark pathological changes in grey matter: extracellular amyloid plaques and neurofibrillary tangles. However, over the past several years, neuroimaging studies have implicated micro- and macrostructural abnormalities in white matter in the risk and progression of AD, suggesting that in addition to the neuronal pathology characteristic of the disease, white matter degeneration and demyelination may be also important pathophysiological features...
March 2, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29423915/sensory-nerve-degeneration-in-a-mouse-model-mimicking-early-manifestations-of-familial-amyloid-polyneuropathy-due-to-transthyretin-ala97ser
#8
H-W Kan, H Chiang, W-M Lin, I-S Yu, S-W Lin, S-T Hsieh
AIMS: Sensory nerve degeneration and consequent abnormal sensations are the earliest and most prevalent manifestations of familial amyloid polyneuropathy (FAP) due to amyloidogenic transthyretin (TTR). FAP is a relentlessly progressive degenerative disease of the peripheral nervous system. However, there is a lack of mouse models to replicate the early neuropathic manifestations of FAP. METHODS: We established human TTR knock-in mice by replacing one allele of the mouse Ttr locus with human wild-type TTR (hTTRwt ) or human TTR with the A97S mutation (hTTRA97S )...
February 8, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29370870/diffusion-kurtosis-imaging-allows-the-early-detection-and-longitudinal-follow-up-of-amyloid-%C3%AE-induced-pathology
#9
Jelle Praet, Nikolay V Manyakov, Leacky Muchene, Zhenhua Mai, Vasilis Terzopoulos, Steve de Backer, An Torremans, Pieter-Jan Guns, Tom Van De Casteele, Astrid Bottelbergs, Bianca Van Broeck, Jan Sijbers, Dirk Smeets, Ziv Shkedy, Luc Bijnens, Darrel J Pemberton, Mark E Schmidt, Annemie Van der Linden, Marleen Verhoye
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly population. In this study, we used the APP/PS1 transgenic mouse model to explore the feasibility of using diffusion kurtosis imaging (DKI) as a tool for the early detection of microstructural changes in the brain due to amyloid-β (Aβ) plaque deposition. METHODS: We longitudinally acquired DKI data of wild-type (WT) and APP/PS1 mice at 2, 4, 6 and 8 months of age, after which these mice were sacrificed for histological examination...
January 9, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29328926/dna-damage-associated-oligodendrocyte-degeneration-precedes-amyloid-pathology-and-contributes-to-alzheimer-s-disease-and-dementia
#10
Kai-Hei Tse, Aifang Cheng, Fulin Ma, Karl Herrup
INTRODUCTION: In looking for novel non-amyloid-based etiologies for Alzheimer's disease, we explore the hypothesis that age-related myelin loss is an attractive explanation for age-associated cognitive decline and dementia. METHODS: We performed a meta-analysis of data in the National Alzheimer's Coordinating Center database accompanied by quantitative histopathology of myelin and oligodendrocytes (OLs) in frontal cortices of 24 clinically characterized individuals...
January 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29273521/the-pathology-and-pathophysiology-of-vascular-dementia
#11
REVIEW
Raj N Kalaria
Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event...
December 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29195086/postmortem-mri-and-histology-demonstrate-differential-iron-accumulation-and-cortical-myelin-organization-in-early-and-late-onset-alzheimer-s-disease
#12
Marjolein Bulk, Walid M Abdelmoula, Rob J A Nabuurs, Linda M van der Graaf, Coen W H Mulders, Aat A Mulder, Carolina R Jost, Abraham J Koster, Mark A van Buchem, Remco Natté, Jouke Dijkstra, Louise van der Weerd
Previous MRI studies reported cortical iron accumulation in early-onset (EOAD) compared to late-onset (LOAD) Alzheimer disease patients. However, the pattern and origin of iron accumulation is poorly understood. This study investigated the histopathological correlates of MRI contrast in both EOAD and LOAD. T2*-weighted MRI was performed on postmortem frontal cortex of controls, EOAD, and LOAD. Images were ordinally scored using predefined criteria followed by histology. Nonlinear histology-MRI registration was used to calculate pixel-wise spatial correlations based on the signal intensity...
February 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29176903/axonal-and-myelinic-pathology-in-5xfad-alzheimer-s-mouse-spinal-cord
#13
Tak-Ho Chu, Karen Cummins, Joseph S Sparling, Shigeki Tsutsui, Craig Brideau, K Peter R Nilsson, Jeffrey T Joseph, Peter K Stys
As an extension of the brain, the spinal cord has unique properties which could allow us to gain a better understanding of CNS pathology. The brain and cord share the same cellular components, yet the latter is simpler in cytoarchitecture and connectivity. In Alzheimer's research, virtually all focus is on brain pathology, however it has been shown that transgenic Alzheimer's mouse models accumulate beta amyloid plaques in spinal cord, suggesting that the cord possesses the same molecular machinery and conditions for plaque formation...
2017: PloS One
https://www.readbyqxmd.com/read/29081415/cortical-iron-reflects-severity-of-alzheimer-s-disease
#14
Sara van Duijn, Marjolein Bulk, Sjoerd G van Duinen, Rob J A Nabuurs, Mark A van Buchem, Louise van der Weerd, Remco Natté
Abnormal iron distribution in the isocortex is increasingly recognized as an in vivo marker for Alzheimer's disease (AD). However, the contribution of iron accumulation to the AD pathology is still poorly understood. In this study, we investigated: 1) frontal cortical iron distribution in AD and normal aging and 2) the relation between iron distribution and degree of AD pathology. We used formalin fixed paraffin embedded frontal cortex from 10 AD patients, 10 elder, 10 middle aged, and 10 young controls and visualized iron with a modified Perl's histochemical procedure...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29070438/humanin-affects-object-recognition-and-gliosis-in-short-term-cuprizone-treated-mice
#15
Minetaka Murakami, Masatoshi Nagahama, Yoichiro Abe, Takako Niikura
Humanin (HN) is a 24-residue peptide that manipulates cell survival under various stresses. A highly potent HN derivative, HNG, reduced amyloid burden and neuroinflammation and suppressed cognitive impairment in Alzheimer's disease model mice. Cuprizone (CPZ), a copper chelator, provokes demyelination in the central nervous system of mice. A shorter (one week) exposure to CPZ induces schizophrenia-like behavior and glial activation prior to demyelination. We tested the effect of HNG on these short-term responses to CZP in mice...
October 14, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28939905/expression-and-differential-responsiveness-of-central-nervous-system-glial-cell-populations-to-the-acute-phase-protein-serum-amyloid-a
#16
Massimo Barbierato, Mila Borri, Laura Facci, Morena Zusso, Stephen D Skaper, Pietro Giusti
Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves hepatic production of acute-phase proteins, including serum amyloid A (SAA). Extrahepatically, SAA immunoreactivity is found in axonal myelin sheaths of cortex in Alzheimer's disease and multiple sclerosis (MS), although its cellular origin is unclear. We examined the responses of cultured rat cortical astrocytes, microglia and oligodendrocyte precursor cells (OPCs) to master pro-inflammatory cytokine tumour necrosis factor (TNF)-α and lipopolysaccaride (LPS)...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844104/co-administration-of-tio2-nanowired-mesenchymal-stem-cells-with-cerebrolysin-potentiates-neprilysin-level-and-reduces-brain-pathology-in-alzheimer-s-disease
#17
Hari Shanker Sharma, Dafin Fior Muresanu, José Vicente Lafuente, Ranjana Patnaik, Z Ryan Tian, Asya Ozkizilcik, Rudy J Castellani, Herbert Mössler, Aruna Sharma
Neprilysin (NPL), the rate-limiting enzyme for amyloid beta peptide (AβP), appears to play a crucial role in the pathogenesis of Alzheimer's disease (AD). Since mesenchymal stem cells (MSCs) and/or cerebrolysin (CBL, a combination of neurotrophic factors and active peptide fragments) have neuroprotective effects in various CNS disorders, we examined nanowired delivery of MSCs and CBL on NPL content and brain pathology in AD using a rat model. AD-like symptoms were produced by intraventricular (i.c.v.) administration of AβP (1-40) in the left lateral ventricle (250 ng/10 μl, once daily) for 4 weeks...
January 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/28766965/map2-ihc-detection-a-marker-of-antigenicity-in-cns-tissues
#18
M R D'Andrea, R J Howanski, C F Saller
Immunohistochemistry (IHC) is used to detect antibody-specific antigens in tissues; the results depend on the ability of the primary antibodies to bind to their antigens. Therefore, results depend on the quality of preservation of the specimen. Many investigators have overcome the deleterious effects of over-fixation on the binding of primary antibodies to specimen antigens using IHC, but if the specimen is under-fixed or fixation is delayed, false negative results could be obtained despite certified laboratory practices...
2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28750656/oligomeric-amyloid-beta-induces-mapk-mediated-activation-of-brain-cytosolic-and-calcium-independent-phospholipase-a-2-in-a-spatial-specific-manner
#19
Juan Pablo Palavicini, Chunyan Wang, Linyuan Chen, Kristen Hosang, Jianing Wang, Takami Tomiyama, Hiroshi Mori, Xianlin Han
Alzheimer's disease (AD) is histopathologically characterized by the build-up of fibrillar amyloid beta (Aβ) in the form of amyloid plaques and the development of intraneuronal neurofibrillary tangles consisting of aggregated hyperphosphorylated Tau. Although amyloid fibrils were originally considered responsible for AD pathogenesis, recent convincing evidence strongly implicates soluble oligomeric Aβ as the primary neurotoxic species driving disease progression. A third largely ignored pathological hallmark, originally described by Alois Alzheimer, is the presence of "adipose inclusions", suggestive of aberrant lipid metabolism...
July 27, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28730955/itraq-based-proteomic-analysis-of-appsw-ind-mice-provides-insights-into-the-early-changes-in-alzheimer-s-disease
#20
Nan Li, Pinghong Hu, Tiantian Xu, Huan Chen, Xiaoying Chen, Jianwen Hu, Xifei Yang, Lei Shi, Jian-Hong Luo, Junyu Xu
BACKGROUND: Several proteins have been identified as potential diagnostic biomarkers in imaging, genetic, or proteomic studies in Alzheimer disease (AD) patients and mouse models. However, biomarkers for presymptom diagnosis of AD are still under investigation, as are the presymptom molecular changes in AD pathogenesis. OBJECTIVE: In this study, we aim to analyzed the early proteomic changes in APPSw,Ind mice and to conduct further functional studies on interesting proteins...
2017: Current Alzheimer Research
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