المؤلفون: Rangan, Priya, Lobo, Fleur, Parrella, Edoardo, Rochette, Nicolas, Morselli, Marco, Stephen, Terri-Leigh, Cremonini, Anna Laura, Tagliafico, Luca, Persia, Angelica, Caffa, Irene, Monacelli, Fiammetta, Odetti, Patrizio, Bonfiglio, Tommaso, Nencioni, Alessio, Pigliautile, Martina, Boccardi, Virginia, Mecocci, Patrizia, Pike, Christian J, Cohen, Pinchas, LaDu, Mary Jo, Pellegrini, Matteo, Xia, Kyle, Tran, Katelynn, Ann, Brandon, Chowdhury, Dolly, Longo, Valter D

المصدر: Cell Reports. 40(13)

مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, Neurosciences, Brain Disorders, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Nutrition, Acquired Cognitive Impairment, Neurodegenerative, Aging, Stem Cell Research, Dementia, Stem Cell Research - Nonembryonic - Non-Human, Neurological, Alzheimer Disease, Amyloid beta-Peptides, Animals, Cognitive Dysfunction, Disease Models, Animal, Fasting, Mice, Mice, Transgenic, NADPH Oxidases, Neuroinflammatory Diseases, Superoxides, tau Proteins, Alzheimer’s disease, CP: Metabolism, CP: Neuroscience, NADPH oxidase, amyloid beta, fasting, fasting-mimicking diet, hyperphosphorylated tau, microglia, neuroinflammation, protein restriction, superoxide, Medical Physiology, Biological sciences

الوصف: The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aβ load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6s41r9ktTest

المؤلفون: Herbert B Allen

المصدر: Journal of Alzheimer's Disease

مصطلحات موضوعية: Pathology, medicine.medical_specialty, biofilm disperser, Plaque, Amyloid, tau Proteins, Inflammation, Penicillins, Disease, Microbiology, Pathogenesis, Alzheimer Disease, Extracellular, Humans, Medicine, Amyloid-β, spirochetes, Borrelia burgdorferi, Neurons, biology, business.industry, General Neuroscience, Biofilm, Brain, Treponema denticola, General Medicine, Hypothesis, biology.organism_classification, Psychiatry and Mental health, Clinical Psychology, penicillin, Toll-like receptor 2, Biofilms, hyperphosphorylated tau, Geriatrics and Gerontology, medicine.symptom, business, Intracellular

الوصف: Utilizing the pathology and microbiology found in tissue from patients with documented Alzheimer’s disease (AD), the pathogenesis of this fateful disorder has been made clear. Borrelia burgdorferi and Treponema denticola spirochetes enter the brain, mostly via neuronal pathways and the entorhinal circulation. These organisms easily pass through the blood-brain barrier and have an affinity for neural tissue. Once in the brain, the spirochetes make intra- and extracellular biofilms, and it is the biofilms that create the pathology. Specifically, it is the intracellular biofilms that are ultimately responsible for neurofibrillary tangles and dendritic disintegration. The extracellular biofilms are responsible for the inflammation that initially is generated by the first responder, Toll-like receptor 2. The hypothesis that arises from this work is two-pronged: one is related to prevention; the other to treatment. Regarding prevention, it is very likely possible that AD could be prevented by periodic administration of penicillin (PCN), which would kill the spirochetes before they made biofilms; this would prevent the disease and would not allow any of the above deleterious changes generated by the biofilms to occur. As regards treatment, it may be possible to slow or prevent further decline in early AD by administration of PCN together with a biofilm disperser. The disperser would disrupt the biofilm coating and enable the PCN to kill the spirochetes. This protocol could be administered in a trial with the control arm utilizing the current treatment. The progress of the treatment could be evaluated by one of the current blood tests that is semi-quantitative. The specific protocols are listed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2b01d384a4b780db443c63019db2a9cTest
https://doi.org/10.3233/jad-210429Test

المؤلفون: Sonja Fixemer, Corrado Ameli, Gaël Hammer, Luis Salamanca, Oihane Uriarte Huarte, Chantal Schwartz, Jean-Jacques Gérardy, Naguib Mechawar, Alexander Skupin, Michel Mittelbronn, David S. Bouvier

المصدر: Acta Neuropathologica Communications, 10

مصطلحات موضوعية: Lewy Body Disease, Amyloid beta-Peptides, tau Proteins, Alzheimer’s disease, Dementia with Lewy Bodies, Hippocampus, Microglia, Amyloid-β, Hyperphosphorylated tau, Phosphorylated α-synuclein, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, Phenotype, nervous system, Alzheimer Disease, alpha-Synuclein, Humans, Neurology (clinical)

الوصف: The cellular alterations of the hippocampus lead to memory decline, a shared symptom between Alzheimer’s disease (AD) and dementia with Lewy Bodies (DLB) patients. However, the subregional deterioration pattern of the hippocampus differs between AD and DLB with the CA1 subfield being more severely affected in AD. The activation of microglia, the brain immune cells, could play a role in its selective volume loss. How subregional microglia populations vary within AD or DLB and across these conditions remains poorly understood. Furthermore, how the nature of the hippocampal local pathological imprint is associated with microglia responses needs to be elucidated. To this purpose, we employed an automated pipeline for analysis of 3D confocal microscopy images to assess CA1, CA3 and DG/CA4 subfields microglia responses in post-mortem hippocampal samples from late-onset AD (n = 10), DLB (n = 8) and age-matched control (CTL) (n = 11) individuals. In parallel, we performed volumetric analyses of hyperphosphorylated tau (pTau), amyloid-β (Aβ) and phosphorylated α-synuclein (pSyn) loads. For each of the 32,447 extracted microglia, 16 morphological features were measured to classify them into seven distinct morphological clusters. Our results show similar alterations of microglial morphological features and clusters in AD and DLB, but with more prominent changes in AD. We identified two distinct microglia clusters enriched in disease conditions and particularly increased in CA1 and DG/CA4 of AD and CA3 of DLB. Our study confirms frequent concomitance of pTau, Aβ and pSyn loads across AD and DLB but reveals a specific subregional pattern for each type of pathology, along with a generally increased severity in AD. Furthermore, pTau and pSyn loads were highly correlated across subregions and conditions. We uncovered tight associations between microglial changes and the subfield pathological imprint. Our findings suggest that combinations and severity of subregional pTau, Aβ and pSyn pathologies transform local microglia phenotypic composition in the hippocampus. The high burdens of pTau and pSyn associated with increased microglial alterations could be a factor in CA1 vulnerability in AD.
Acta Neuropathologica Communications, 10
ISSN:2051-5960

وصف الملف: application/application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::18cb3f3952d6f80b3e6009fbf173f3aaTest
https://pubmed.ncbi.nlm.nih.gov/35296366Test

المؤلفون: Souchet, B., Audrain, M., Gu, Y., Lindberg, M. F., Orefice, Nicola Salvatore, Rey, E., Cartier, N., Janel, N., Meijer, L., Braudeau, J.

المساهمون: Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris-Saclay, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), AP-HP. Université Paris Saclay, ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011)

المصدر: ISSN: 2274-5807.

مصطلحات موضوعية: Animals, Humans, Rats, Alzheimer Disease, DYRK1A, AAV-AD rat, Amyloid beta-Peptides, Aβ42, Cognitive Dysfunction, Hyperphosphorylated tau, leucettine, mild cognitive impairment, Peptide Fragments, Prodromal Symptoms, tau Proteins, [SDV]Life Sciences [q-bio]

الوصف: International audience ; BACKGROUND: Alzheimer's disease (AD) is a continuum of events beginning with an increase in brain soluble Aβ42 followed by the appearance of hyperphosphorylated tau (P-tau, asymptomatic stage). Mild Cognitive Impairment (MCI) then appears (prodromal stage). However, the individual contribution of these two soluble proteins in the onset of the first cognitive symptoms remains unclear. OBJECTIVES: We sought to understand the specific impact of p-tau on the development of MCI in the AAV-AD rat model, a model of late-onset Alzheimer's disease (LOAD) predementia. METHODS: We specifically reduced the phosphorylation level of tau while leaving Aβ42 levels unchanged using a DYRK1A protein kinase inhibitor, Leucettine L41, in an adeno-associated virus-based Alzheimer's disease (AAV-AD) rat model. Leucettine L41 was administered by intraperitoneal injection at 20 mg/kg per day in AAV-AD rats from 9 (late asymptomatic phase) to 10 (prodromal phase) months of age. RESULTS: Decreased soluble forms of P-tau induced by chronic administration of Leucettine L41 did not change soluble Aβ42 levels but prevented MCI onset in 10-month-old AAV-AD rats. CONCLUSIONS: The present study argues that P-tau is required to induce the development of MCI. Consistent with our previous findings that soluble Aβ42 is also required for MCI onset, the data obtained in the AAV-AD rat model confirm that the transition from the asymptomatic to the prodromal stage may be caused by the combined presence of both soluble brain forms of Aβ42 and p-tau, suggesting that the development of MCI may be the consequence of their synergistic action.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35841249; hal-04281622; https://cnrs.hal.science/hal-04281622Test; PUBMED: 35841249

الإتاحة: https://doi.org/10.14283/jpad.2022.18Test
https://cnrs.hal.science/hal-04281622Test

المؤلفون: Angela Everhart, Carol A. Colton, Kirby W Gottschalk, Michael P. Vitek, Audra York

المصدر: ASN NEURO
ASN Neuro, Vol 13 (2021)

مصطلحات موضوعية: 0301 basic medicine, Male, Arginine, Apolipoprotein E4, Neurosciences. Biological psychiatry. Neuropsychiatry, tau Proteins, Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Alzheimer Disease, Gene expression, Humans, Phosphorylation, differential gene expression, Gene, Neurons, Original Paper, Methionine, General Neuroscience, Metabolism, radical s-adenosyl domain 1, APOE and sex based changes, Cell biology, Metabolic pathway, 030104 developmental biology, chemistry, brain metabolism, biology.protein, hyperphosphorylated tau, Immunohistochemistry, Female, Neurology (clinical), NeuN, 030217 neurology & neurosurgery, RC321-571

الوصف: Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-mediated neuronal processes in brain using isolated neurons derived from human autopsy brain sections of normal individuals and individuals diagnosed as Alzheimer’s disease (AD). Laser capture microscopy was used to select specific cell types in immune-stained thin brain sections followed by NanoString technology to identify and quantify differences in mRNA levels between age-matched control and AD neuronal samples. Comparisons were also made between neurons isolated from AD brain sections expressing pathogenic hyperphosphorylated AT8- positive (AT8+) tau and non-AT8+ AD neurons using double labeling techniques. The mRNA expression data showed unique patterns of metabolic pathway expression between the subtypes of captured neurons that involved membrane based solute transporters, redox factors, and arginine and methionine metabolic pathways. We also identified the expression levels of a novel metabolic gene, Radical-S-Adenosyl Domain1 ( RSAD1) and its corresponding protein, Rsad1, that impact methionine usage and radical based reactions. Immunohistochemistry was used to identify specific protein expression levels and their cellular location in NeuN+ and AT8+ neurons. APOE4 vs APOE3 genotype-specific and sex-specific gene expression differences in these metabolic pathways were also observed when comparing neurons from individuals with AD to age-matched individuals.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::666cffab2c00b0dd3a93b5f25eee7578Test
http://europepmc.org/articles/PMC8207264Test

المؤلفون: Luca Russo, Luana Fioriti, Carmina Natale, Elisa R. Zanier, Roberto Chiesa, Luisa Diomede, Maria Monica Barzago, Elena Restelli, Gloria Vegliante, Laura Colombo, Luca Colnaghi, Edoardo Micotti, Margherita Romeo, Ilaria Bertani

المصدر: Neurobiology of Disease, Vol 153, Iss, Pp 105330-(2021)
Neurobiology of Disease

مصطلحات موضوعية: 0301 basic medicine, Genetically modified mouse, Aβ, amyloid β, Traumatic brain injury, Neuromuscular Junction, Neuromuscular transmission, tau Proteins, Motor Activity, Biology, Article, TBI, traumatic brain injury, lcsh:RC321-571, TauP301L, recombinant tau with the P301L mutation, Mice, 03 medical and health sciences, 0302 clinical medicine, Brain Injuries, Traumatic, medicine, Animals, Neuromuscular synaptic transmission, Cognitive decline, NGM, nematode growth medium, Caenorhabditis elegans, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, p-tau, hyperphosphorylated tau, KO, knockout, PK, proteinase-K, SNAP, simple neuroassessment of asymmetric impairment, Non-Tg, non-transgenic, Neurodegeneration, TBIcontra, tissue from contralateral brain area of TBI mice, Neurodegenerative Diseases, medicine.disease, WT, wild-type, Cell biology, Tauopathy, 030104 developmental biology, Tauopathies, Neurology, Toxicity, tauTBI, TBI-induced abnormal form of tau, TauWT, recombinant wild-type tau, TBIipsi, tissue from ipsilateral brain area of TBI mice, Tau, 030217 neurology & neurosurgery, Contra, contralateral

الوصف: Traumatic brain injury (TBI) is associated with widespread tau pathology in about 30% of patients surviving late after injury. We previously found that TBI in mice induces the formation of an abnormal form of tau (tauTBI) which progressively spreads from the site of injury to remote brain regions. Intracerebral inoculation of TBI brain homogenates into naïve mice induced progressive tau pathology, synaptic loss and late cognitive decline, suggesting a pivotal role of tauTBI in post-TBI neurodegeneration. However, the possibility that tauTBI was a marker of TBI-associated neurodegeneration rather than a toxic driver of functional decline could not be excluded. Here we employed the nematode C. elegans as a biosensor to test the pathogenic role of TBI generated tau. The motility of this nematode depends on efficient neuromuscular transmission and is exceptionally sensitive to the toxicity of amyloidogenic proteins, providing a tractable model for our tests. We found that worms exposed to brain homogenates from chronic but not acute TBI mice, or from mice in which tauTBI had been transmitted by intracerebral inoculation, had impaired motility and neuromuscular synaptic transmission. Results were similar when worms were given brain homogenates from transgenic mice overexpressing tau P301L, a tauopathy mouse model, suggesting that TBI-induced and mutant tau have similar toxic properties. P301L brain homogenate toxicity was similar in wild-type and ptl-1 knock-out worms, indicating that the nematode tau homolog protein PTL-1 was not required to mediate the toxic effect. Harsh protease digestion to eliminate the protein component of the homogenates, pre-incubation with anti-tau antibodies or tau depletion by immunoprecipitation, abolished the toxicity. Homogenates of chronic TBI brains from tau knock-out mice were not toxic to C. elegans, whereas oligomeric recombinant tau was sufficient to impair their motility. This study indicates that tauTBI impairs motor activity and synaptic transmission in C. elegans and supports a pathogenic role of tauTBI in the long-term consequences of TBI. It also sets the groundwork for the development of a C. elegans-based platform for screening anti-tau compounds.
Graphical abstract Unlabelled Image
Highlights • Traumatic brain injury (TBI) in mice induces a progressive tau pathology. • Brain-injured tissue from chronic but not acute TBI mice impairs C. elegans motility. • TBI tissue immunodepleted of tau or from tau knock-out mice has no toxic effect. • Brain-injured tissue from TBI mice impairs neuromuscular transmission in worms. • C. elegans is a tractable model for investigating tau toxicity generated by TBI.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::241bd53568f58354b57cccba9cff43e8Test
http://www.sciencedirect.com/science/article/pii/S0969996121000796Test

المؤلفون: Zahinoor Ismail, Nagaendran Kandiah, Serge Gauthier, Pedro Rosa-Neto, Hui Chiew, Kok Pin Ng

المصدر: Translational Neurodegeneration, Vol 10, Iss 1, Pp 1-14 (2021)
Translational Neurodegeneration

مصطلحات موضوعية: Oncology, medicine.medical_specialty, Neurology, Cognitive Neuroscience, Prodromal Symptoms, Mild behavioral impairment, tau Proteins, Review, Disease, lcsh:RC346-429, Amyloid beta-Protein Precursor, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Atrophy, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Cognitive Dysfunction, Amyloid-β, Hyperphosphorylated tau, Neurodegeneration, Cognitive decline, Pathological, health care economics and organizations, Preclinical Alzheimer’s disease, lcsh:Neurology. Diseases of the nervous system, 030214 geriatrics, business.industry, Mental Disorders, technology, industry, and agriculture, medicine.disease, Pathophysiology, Neuropsychiatric symptoms, Anxiety, Neurology (clinical), Nervous System Diseases, medicine.symptom, business, 030217 neurology & neurosurgery

الوصف: The development of in vivo biomarkers of Alzheimer’s disease (AD) has advanced the diagnosis of AD from a clinical syndrome to a biological construct. The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals. While neuropsychiatric symptoms (NPS) are non-cognitive symptoms that are increasingly recognized as early manifestations of AD, the associations of NPS with AD pathophysiology in preclinical AD remain unclear. Here, we review the associations between NPS and AD biomarkers amyloid-β (Aβ), tau and neurodegeneration in preclinical AD and cognitively-unimpaired individuals in 19 eligible English-language publications (8 cross-sectional studies, 10 longitudinal, 1 both cross-sectional and longitudinal). The cross-sectional studies have consistently shown that NPS, particularly depressive and anxiety symptoms, are associated with higher Aβ. The longitudinal studies have suggested that greater NPS are associated with higher Aβ and cognitive decline in cognitively unimpaired subjects over time. However, most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau pathology. For the association of NPS and neurodegeneration, two studies have shown that the cerebrospinal fluid total-tau is linked to longitudinal increase in NPS and that the NPS may predict longitudinal metabolic decline in preclinical AD, respectively. However, evidence for the association between atrophy and NPS in preclinical AD is less consistent. Therefore, future longitudinal studies with well-designed methodologies and NPS measurements are required not only to determine the relationship among AT(N) biomarkers, NPS and cognitive decline, but also to elucidate the contribution of comorbid pathology to preclinical AD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0ee8befeadc8acd1b77578bf1b2b25cTest
https://doi.org/10.1186/s40035-021-00236-3Test

المؤلفون: Priya Rangan, Fleur Lobo, Edoardo Parrella, Nicolas Rochette, Marco Morselli, Terri-Leigh Stephen, Anna Laura Cremonini, Luca Tagliafico, Angelica Persia, Irene Caffa, Fiammetta Monacelli, Patrizio Odetti, Tommaso Bonfiglio, Alessio Nencioni, Martina Pigliautile, Virginia Boccardi, Patrizia Mecocci, Christian J. Pike, Pinchas Cohen, Mary Jo LaDu, Matteo Pellegrini, Kyle Xia, Katelynn Tran, Brandon Ann, Dolly Chowdhury, Valter D. Longo

المصدر: Cell reports, vol 40, iss 13

مصطلحات موضوعية: Aging, fasting, Medical Physiology, microglia, Mice, Transgenic, tau Proteins, Neurodegenerative, Alzheimer's Disease, General Biochemistry, Genetics and Molecular Biology, Transgenic, neuroinflammation, Mice, Alzheimer Disease, Superoxides, Acquired Cognitive Impairment, Animals, protein restriction, Cognitive Dysfunction, Nutrition, Amyloid beta-Peptides, NADPH oxidase, Animal, Neuroscience [CP], Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), NADPH Oxidases, Fasting, Stem Cell Research, CP: Metabolism, fasting-mimicking diet, Brain Disorders, amyloid beta, Disease Models, Animal, Metabolism [CP], CP: Neuroscience, Disease Models, Neurological, Neuroinflammatory Diseases, hyperphosphorylated tau, Dementia, Stem Cell Research - Nonembryonic - Non-Human, superoxide, Biochemistry and Cell Biology, Alzheimer’s disease

الوصف: The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aβ load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc0b3f9d83e2f452146e6103295d13c7Test
https://pubmed.ncbi.nlm.nih.gov/36170815Test

المؤلفون: Anton Meinicke, Wolfgang Härtig, Karsten Winter, Joana Puchta, Bianca Mages, Dominik Michalski, Alexander Emmer, Markus Otto, Karl-Titus Hoffmann, Willi Reimann, Matthias Krause, Stefan Schob

المصدر: Biomolecules; Volume 12; Issue 1; Pages: 96
Biomolecules
Biomolecules, Vol 12, Iss 96, p 96 (2022)

مصطلحات موضوعية: 3xTg mouse, hippocampus, Mice, Transgenic, tau Proteins, Microbiology, Biochemistry, Article, Mice, Surface-Active Agents, Alzheimer Disease, ddc:570, SP-G, Animals, Humans, Alzheimer’s disease, SFTA2, habenula, Reelin, β-amyloid, hyperphosphorylated tau, Molecular Biology, Amyloid beta-Peptides, Pulmonary Surfactant-Associated Protein A, Brain, QR1-502, Disease Models, Animal

الوصف: The classic surfactant proteins (SPs) A, B, C, and D were discovered in the lungs, where they contribute to host defense and regulate the alveolar surface tension during breathing. Their additional importance for brain physiology was discovered decades later. SP-G, a novel amphiphilic SP, was then identified in the lungs and is mostly linked to inflammation. In the brain, it is also present and significantly elevated after hemorrhage in premature infants and in distinct conditions affecting the cerebrospinal fluid circulation of adults. However, current knowledge on SP-G-expression is limited to ependymal cells and some neurons in the subventricular and superficial cortex. Therefore, we primarily focused on the distribution of SP-G-immunoreactivity (ir) and its spatial relationships with components of the neurovascular unit in murine forebrains. Triple fluorescence labeling elucidated SP-G-co-expressing neurons in the habenula, infundibulum, and hypothalamus. Exploring whether SP-G might play a role in Alzheimer’s disease (AD), 3xTg-AD mice were investigated and displayed age-dependent hippocampal deposits of β-amyloid and hyperphosphorylated tau separately from clustered, SP-G-containing dots with additional Reelin-ir—which was used as established marker for disease progression in this specific context. Semi-quantification of those dots, together with immunoassay-based quantification of intra- and extracellular SP-G, revealed a significant elevation in old 3xTg mice when compared to age-matched wildtype animals. This suggests a role of SP-G for the pathophysiology of AD, but a confirmation with human samples is required.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::81ea76c82f477a1cb4d0724868fe4787Test
https://doi.org/10.3390/biom12010096Test

المؤلفون: Patrick Kwan, Nigel C. Jones, Runxuan Lin

المصدر: International Journal of Molecular Sciences, Vol 21, Iss 3676, p 3676 (2020)
International Journal of Molecular Sciences

مصطلحات موضوعية: Amyloid beta, Tau protein, tau Proteins, Review, Epileptogenesis, Catalysis, Inorganic Chemistry, lcsh:Chemistry, Epilepsy, Amyloid beta-Protein Precursor, GSK-3, Alzheimer Disease, Seizures, medicine, Amyloid precursor protein, Dementia, Animals, Humans, Hyperphosphorylated tau, Physical and Theoretical Chemistry, Glycogen synthase, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, biology, Organic Chemistry, General Medicine, medicine.disease, Epileptic seizures, Computer Science Applications, Glycogen synthase kinase 3, lcsh:Biology (General), lcsh:QD1-999, biology.protein, Neuroscience, Alzheimer’s disease

الوصف: Alzheimer’s disease (AD) is the most common form of dementia. An increasing body of evidence describes an elevated incidence of epilepsy in patients with AD, and many transgenic animal models of AD also exhibit seizures and susceptibility to epilepsy. However, the biological mechanisms that underlie the occurrence of seizure or increased susceptibility to seizures in AD is unknown. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that regulates various cellular signaling pathways, and plays a crucial role in the pathogenesis of AD. It has been suggested that GSK-3 might be a key factor that drives epileptogenesis in AD by interacting with the pathological hallmarks of AD, amyloid precursor protein (APP) and tau. Furthermore, seizures may also contribute to the progression of AD through GSK-3. In this way, GSK-3 might be involved in initiating a vicious cycle between AD and seizures. This review aims to summarise the possible role of GSK-3 in the link between AD and seizures. Understanding the role of GSK-3 in AD-associated seizures and epilepsy may help researchers develop new therapeutic approach that can manage seizure and epilepsy in AD patients as well as decelerate the progression of AD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c10a93faa96f6fa14151bdeb0ef6fe49Test
https://www.mdpi.com/1422-0067/21/10/3676Test