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https://www.readbyqxmd.com/read/29346315/dietary-total-prenylflavonoids-from-the-fruits-of-psoralea-corylifolia-l-prevents-age-related-cognitive-deficits-and-down-regulates-alzheimer-s-markers-in-samp8-mice
#1
Zhi-Jing Chen, Yan-Fang Yang, Ying-Tao Zhang, Dong-Hui Yang
Alzheimer's disease (AD) is a serious threat for the aging society. In this study, we examined the preventive effect of the total prenylflavonoids (TPFB) prepared from the dried fruits of Psoralea corylifolia L., using an age-related AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg·day significantly improved cognitive performance of the SAMP8 mice in Morris water maze tests, similar to 150 mg/kg·day of resveratrol, a popular neuro-protective compound. Furthermore, TPFB treatment showed significant improvements in various AD markers in SAMP8 brains, which were restored to near control levels of the normal mice, SAMR1...
January 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29345054/isoflurane-anesthesia-in-aged-mice-and-effects-of-a1-adenosine-receptors-on-cognitive-impairment
#2
Chun-Long Zuo, Chun-Man Wang, Jin Liu, Ting Shen, Jiang-Ping Zhou, Xin-Rui Hao, Yi-Zhao Pan, Hua-Cheng Liu, Qing-Quan Lian, Han Lin
AIMS: Isoflurane may not only accelerate the process of Alzheimer's disease (AD), but increase the risk of incidence of postoperative cognitive dysfunction (POCD). However, the underlying mechanisms remain unknown. This study was designed to investigate whether isoflurane contributed to the POCD occurrence through A1 adenosine receptor (A1AR) in aged mice. METHODS: We assessed cognitive function of mice with Morris water maze (MWM) and then measured expression level of two AD biomarkers (P-tau and Aβ) and a subtype of the NMDA receptor (NR2B) in aged wild-type (WT) and homozygous A1 adenosine receptor (A1AR) knockout (KO) mice at baseline and after they were exposed to isoflurane (1...
January 17, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29338612/gene-profiling-of-nucleus-basalis-tau-containing-neurons-in-chronic-traumatic-encephalopathy-a-chronic-effects-of-neurotrauma-consortium-study
#3
Elliott Jay Mufson, Bin He, Stephen D Ginsberg, Benjamin A Carper, Gayle S Bieler, Fiona C Crawford, Victor E Alverez, Bernard R Huber, Thor D Stein, Ann C McKee, Sylvia E Perez
Military personnel and athletes exposed to traumatic brain injury may develop chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the main constituent of neurofibrillary tangles (NFTs). Recently, we found that cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert (nbM), which provide the major cholinergic innervation to the cortex, display an increasing number of NFTs across the pathological stages of CTE...
January 16, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29332046/a-novel-antibody-targeting-tau-phosphorylated-at-serine-235-detects-neurofibrillary-tangles
#4
David Brici, Jürgen Götz, Rebecca M Nisbet
Alzheimer's disease is characterized by two main pathological hallmarks in the human brain: the extracellular deposition of amyloid-β as plaques and the intracellular accumulation of the hyperphosphorylated protein tau as neurofibrillary tangles (NFTs). Phosphorylated tau (p-tau) specific-antibodies and silver staining have been used to reveal three morphological stages of NFT formation: pre-NFTs, intraneuronal NFTs (iNFTs), and extraneuronal NFTs (eNFTs). Here we characterize a novel monoclonal antibody, RN235, which is specific for tau phosphorylated at serine 235, and detects iNFTs and eNFTs in brain tissue, suggesting that phosphorylation at this site is indicative of late stage changes in tau...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29331877/cerebral-changes-and-disrupted-gray-matter-cortical-networks-in-asymptomatic-older-adults-at-risk-for-alzheimer-s-disease
#5
Jose L Cantero, Mercedes Atienza, Pascual Sanchez-Juan, Eloy Rodriguez-Rodriguez, Jose Luis Vazquez-Higuera, Ana Pozueta, Andrea Gonzalez-Suarez, Eduard Vilaplana, Jordi Pegueroles, Victor Montal, Rafael Blesa, Daniel Alcolea, Alberto Lleo, Juan Fortea
The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established in Alzheimer's disease, but our current knowledge about how abnormal CSF levels affect cerebral integrity, at local and network levels, is incomplete in asymptomatic older adults. Here, we have collected CSF samples and performed structural magnetic resonance imaging scans in cognitively normal elderly as part of a cross-sectional multicenter study (SIGNAL project). To identify group differences in cortical thickness, white matter volume, and properties of structural networks, participants were split into controls (N = 20), positive amyloid-β (Aβ1-42+) (N = 19), and positive phosphorylated tau (N = 18)...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29331876/app-go-protein-g%C3%AE-%C3%AE-complex-signaling-mediates-a%C3%AE-degeneration-and-cognitive-impairment-in-alzheimer-s-disease-models
#6
Elena Anahi Bignante, Nicolás Eric Ponce, Florencia Heredia, Juliana Musso, María C Krawczyk, Julieta Millán, Gustavo F Pigino, Nibaldo C Inestrosa, Mariano M Boccia, Alfredo Lorenzo
Deposition of amyloid-β (Aβ), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism of Aβ-induced degeneration in AD remains on debate. Here, we analyzed the interaction of APP with heterotrimeric Go protein in primary hippocampal cultures and found that Aβ deposition dramatically enhanced APP-Go protein interaction in dystrophic neurites. APP overexpression rendered neurons vulnerable to Aβ toxicity by a mechanism that required Go-Gβγ complex signaling and p38-mitogen-activated protein kinase activation...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29328927/alzheimer-s-disease-biomarker-guided-diagnostic-workflow-using-the-added-value-of-six-combined-cerebrospinal-fluid-candidates-a%C3%AE-1-42-total-tau-phosphorylated-tau-nfl-neurogranin-and-ykl-40
#7
Harald Hampel, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Remy Genthon, Bruno Dubois, Roberto Floris, Francesco Garaci, Simone Lista
INTRODUCTION: The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation...
January 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29324921/the-correlation-of-evans-index-with-csf-protein-levels-and-ventriculomegaly
#8
D Papaoikonomou, E Karypidou, P Megagiannis, F Tsolaki-Tagaraki, S Nenopoulou, O Gkatzima, Magda Tsolaki
OBJECTIVE: The role of ventriculomegaly and its interplay between various dementia entities and their pathogenesis, as well as its correlation to the levels of CSF protein markers, remains to be elucidated. Evans index (EI) is a well-established radiological marker in the diagnosis of idiopathic Normal Pressure Hydrocephalus (iNPH), assessing ventricular enlargement. However, there are no previous studies investigating the correlation between EI, age, beta amyloid (Aβ), tau and phosphorylated-tau (p-tau) proteins in the CSF...
September 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29321235/comparing-18f-av-1451-with-csf-t-tau-and-p-tau-for-diagnosis-of-alzheimer-disease
#9
Niklas Mattsson, Ruben Smith, Olof Strandberg, Sebastian Palmqvist, Michael Schöll, Philip S Insel, Douglas Hägerström, Tomas Ohlsson, Henrik Zetterberg, Kaj Blennow, Jonas Jögi, Oskar Hansson
OBJECTIVE: To compare PET imaging of tau pathology with CSF measurements (total tau [t-tau] and phosphorylated tau [p-tau]) in terms of diagnostic performance for Alzheimer disease (AD). METHODS: We compared t-tau and p-tau and 18F-AV-1451 in 30 controls, 14 patients with prodromal AD, and 39 patients with Alzheimer dementia, recruited from the Swedish BioFINDER study. All patients with AD (prodromal and dementia) were screened for amyloid positivity using CSF β-amyloid 42...
January 10, 2018: Neurology
https://www.readbyqxmd.com/read/29314492/the-binding-mode-of-a-repeat-like-tau-sequence-with-tubulin
#10
Harindranath Kadavath, Yunior Cabrales Fontela, Mariusz Jaremko, Lukasz Jaremko, Kerstin Overkamp, Jacek Biernat, Eckhard Mandelkow, Markus Zweckstetter
The microtubule-associated protein Tau promotes the polymerization of tubulin and modulates the function of microtubules. Because of the dynamic nature of the Tau/tubulin interaction, the structural basis of this complex has remained largely elusive. Using a combination of NMR methods optimized for ligand-receptor interactions and site-directed mutagenesis we demonstrate that the flanking domain downstream of the four microtubule-binding repeats of Tau binds competitively to a site on the α-tubulin surface...
January 3, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29298849/pathologic-thr175-tau-phosphorylation-in-cte-and-cte-with-als
#11
Alexander J Moszczynski, Wendy Strong, Kathy Xu, Ann McKee, Arthur Brown, Michael J Strong
OBJECTIVE: To investigate whether chronic traumatic encephalopathy (CTE) and CTE with amyotrophic lateral sclerosis (CTE-ALS) exhibit features previously observed in other tauopathies of pathologic phosphorylation of microtubule-associated protein tau at Thr175 (pThr175 tau) and Thr231 (pThr231 tau), and glycogen synthase kinase-3β (GSK3β) activation, and whether these pathologic features are a consequence of traumatic brain injury (TBI). METHODS: Tau isoform expression was assayed by western blot in 6 stage III CTE cases...
January 3, 2018: Neurology
https://www.readbyqxmd.com/read/29289286/abnormal-energy-metabolism-and-tau-phosphorylation-in-the-brains-of-middle-aged-mice-in-response-to-atmospheric-pm2-5-exposure
#12
Rui Gao, Tingting Ku, Xiaotong Ji, Yingying Zhang, Guangke Li, Nan Sang
In light of the accelerated aging of the global population and the deterioration of the atmosphere pollution, we sought to clarify the potential mechanisms by which fine particulate matter (PM2.5) can cause cognitive impairment and neurodegeneration through the alteration of mitochondrial structure and function. The results indicate that PM2.5 inhalation reduces ATP production by disrupting the aerobic tricarboxylic acid cycle and oxidative phosphorylation, thereby causing the hypophosphorylation of tau in the cortices of middle-aged mice...
December 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/29286334/a-single-neonatal-exposure-to-bmaa-in-a-rat-model-produces-neuropathology-consistent-with-neurodegenerative-diseases
#13
Laura Louise Scott, Timothy Grant Downing
Although cyanobacterial β-N-methylamino-l-alanine (BMAA) has been implicated in the development of Alzheimer's Disease (AD), Parkinson's Disease (PD) and Amyotrophic Lateral Sclerosis (ALS), no BMAA animal model has reproduced all the neuropathology typically associated with these neurodegenerative diseases. We present here a neonatal BMAA model that causes β-amyloid deposition, neurofibrillary tangles of hyper-phosphorylated tau, TDP-43 inclusions, Lewy bodies, microbleeds and microgliosis as well as severe neuronal loss in the hippocampus, striatum, substantia nigra pars compacta, and ventral horn of the spinal cord in rats following a single BMAA exposure...
December 29, 2017: Toxins
https://www.readbyqxmd.com/read/29286086/microrna-107-prevents-amyloid-%C3%AE-induced-neurotoxicity-and-memory-impairment-in-mice
#14
Bohui Shu, Xiaoyan Zhang, Ganqin Du, Qizhi Fu, Lina Huang
The pathogenesis of Alzheimer's disease (AD) has still not been fully elucidated, however it is thought that the build up of amyloid plaque at least partially causes the symptoms of AD. MicroRNAs (miRNAs) are endogenous non‑coding small RNA molecules that regulate the expression and degradation of proteins. The present study induced symptoms of AD in mice via intraventricular injection of amyloid‑β 1‑42 (Aβ1‑42), which decreased levels of miR‑107. However, miR‑107 levels increased following administration of miR‑107 mimic, a double‑stranded RNA molecule designed to imitate the native miRNA...
December 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29284531/cerebrovascular-and-amyloid-pathology-in-predementia-stages-the-relationship-with-neurodegeneration-and-cognitive-decline
#15
Isabelle Bos, Frans R Verhey, Inez H G B Ramakers, Heidi I L Jacobs, Hilkka Soininen, Yvonne Freund-Levi, Harald Hampel, Magda Tsolaki, Åsa K Wallin, Mark A van Buchem, Ania Oleksik, Marcel M Verbeek, Marcel Olde Rikkert, Wiesje M van der Flier, Philip Scheltens, Pauline Aalten, Pieter Jelle Visser, Stephanie J B Vos
BACKGROUND: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia. METHODS: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies...
December 29, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29282774/adult-moyamoya-disease-associated-with-abundant-phosphorylated-tau-accumulation-in-the-brainstem-report-of-a-case-with-autopsy-findings
#16
Koichi Okamoto, Isao Naito, Toshio Fukuda, Keiji Suzuki, Masamitsu Takatama
We report the case of a 72-year-old Japanese woman with moyamoya disease (MMD). She experienced her first intracerebral hemorrhage (ICH) at the age of 32 years, and had nine ICHs and/or intraventricular hemorrhages during the following 40 years. Cerebral angiograms and vascular pathologies at autopsy confirmed that the patient suffered from MMD. Macroscopically, there were brown-colored changes in the subarachnoid space, mainly at the base of the brain and around the cerebellar hemispheres. Microscopically, hemosiderin deposits were observed mainly in the old hemorrhagic lesions and on the surface of the brainstem and cerebellum...
December 27, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29282410/cerebrospinal-fluid-s100b-and-alzheimer-s-disease-biomarkers-in-hip-fracture-patients-with-delirium
#17
Karen Roksund Hov, Nils Bolstad, Ane-Victoria Idland, Henrik Zetterberg, Kaj Blennow, Farrukh A Chaudhry, Frede Frihagen, Johan Ræder, Torgeir Bruun Wyller, Leiv Otto Watne
Objectives: This study aimed to investigate the relationship between cerebrospinal fluid (CSF) S100B astrocyte-derived protein and delirium and to perform stratified analyses according to clinical and CSF markers of dementia. Methods: We performed a prospective cohort study in a university hospital setting. The participants were patients admitted for hip fracture (n = 98) or for elective surgery (n = 50). Delirium was assessed daily perioperatively in hip fracture patients using the Confusion Assessment Method...
September 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/29282337/associations-between-18f-av1451-tau-pet-and-csf-measures-of-tau-pathology-in-a-clinical-sample
#18
Renaud La Joie, Alexandre Bejanin, Anne M Fagan, Nagehan Ayakta, Suzanne L Baker, Viktoriya Bourakova, Adam L Boxer, Jungho Cha, Anna Karydas, Gina Jerome, Anne Maass, Ashley Mensing, Zachary A Miller, James P O'Neil, Julie Pham, Howard J Rosen, Richard Tsai, Adrienne V Visani, Bruce L Miller, William J Jagust, Gil D Rabinovici
OBJECTIVE: To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample. METHODS: Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([18F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ42, total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3)...
December 27, 2017: Neurology
https://www.readbyqxmd.com/read/29282336/csf-neurofilament-light-chain-and-phosphorylated-tau-181-predict-disease-progression-in-psp
#19
Julio C Rojas, Jee Bang, Iryna V Lobach, Richard M Tsai, Gil D Rabinovici, Bruce L Miller, Adam L Boxer
OBJECTIVE: To determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP). METHODS: We compared the ability of baseline CSF β-amyloid1-42, tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, to predict 52-week changes in clinical (PSP Rating Scale [PSPRS] and Schwab and England Activities of Daily Living [SEADL]), neuropsychological, and regional brain volumes on MRI using linear mixed effects models controlled for age, sex, and baseline disease severity, and Fisher F density curves to compare effect sizes in 50 patients with PSP...
December 27, 2017: Neurology
https://www.readbyqxmd.com/read/29281045/protein-phosphatase-2a-and-its-methylation-modulating-enzymes-lcmt-1-and-pme-1-are-dysregulated-in-tauopathies-of-progressive-supranuclear-palsy-and-alzheimer-disease
#20
Hye-Jin Park, Kang-Woo Lee, Stephanie Oh, Run Yan, Jie Zhang, Thomas G Beach, Charles H Adler, Michael Voronkov, Steven P Braithwaite, Jeffry B Stock, M Maral Mouradian
Hyperphosphorylated tau aggregates are characteristic of tauopathies including progressive supranuclear palsy (PSP) and Alzheimer disease (AD), but factors contributing to pathologic tau phosphorylation are not well understood. Here, we studied the regulation of the major tau phosphatase, the heterotrimeric AB55αC protein phosphatase 2 A (PP2A), in PSP and AD. The assembly and activity of this PP2A isoform are regulated by reversible carboxyl methylation of its catalytic C subunit, while the B subunit confers substrate specificity...
December 21, 2017: Journal of Neuropathology and Experimental Neurology
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