RESUMO
We present a series of 10 hospitalized patients with confirmed coronavirus 2019 infections who developed severe neurovascular complications and discuss the possible reasons for these findings and their relationship to the novel Severe Acute Respiratory Syndrome coronavirus 2 infection.
Assuntos
Betacoronavirus , Transtornos Cerebrovasculares/etiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Adulto , Idoso , COVID-19 , Transtornos Cerebrovasculares/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
We describe 2 hospitalized patients with confirmed coronavirus 19 (COVID-19) infection in whom brain imaging showed hemorrhagic posterior reversible encephalopathy syndrome, and we discuss the possible reasons for these findings and their relationship to the infection.
Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Hemorragias Intracranianas/diagnóstico por imagem , Pneumonia Viral/complicações , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Idoso , COVID-19 , Feminino , Humanos , Hemorragias Intracranianas/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pandemias , Síndrome da Leucoencefalopatia Posterior/etiologia , SARS-CoV-2RESUMO
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RESUMO
TAU mutations are genetically linked to fronto-temporal dementia (FTD) and hyper-phosphorylated aggregates of Tau form neurofibrillary tangles (NFTs) that constitute a pathological hallmark of Alzheimer disease (AD) and FTD. These observations indicate that Tau has a pivotal role in the pathogenesis of neurodegenerative disorders. Tau is cleaved by caspases at Aspartate421, to form a Tau metabolite known as δTau; δTau is increased in AD, due to the hyper-activation of caspases in AD brains. δTau is considered a critical toxic moiety underlying neurodegeneration, which initiates and facilitates NFT formation. As Tau is a therapeutic target in neurodegeneration, it is important to rigorously determine whether δTau is a toxic Tau species that should be pharmacologically attacked. To directly address these questions, we have generated a knock-in (KI) mouse called TauDN-that expresses a Tau mutant that cannot be cleaved by caspases. TauDN mice present short-term memory deficits and synaptic plasticity defects. Moreover, mice carrying two mutant Tau alleles show increased total insoluble hyper-phosphorylated Tau in the forebrain. These data are in contrast with the concept that δTau is a critical toxic moiety underlying neurodegeneration, and suggest that cleavage of Tau by caspases represents a negative feedback mechanism aimed to eliminate toxic Tau species. Alternatively, it is possible that either a reduction or an increase in δTau leads to synaptic dysfunction, memory impairments and Tau pathology. Both possibilities will have to be considered when targeting caspase cleavage of Tau in AD therapy.
Assuntos
Ácido Aspártico/metabolismo , Encéfalo/metabolismo , Caspases/metabolismo , Transtornos da Memória/metabolismo , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Proteínas tau/metabolismo , Animais , Comportamento Animal/fisiologia , Encéfalo/patologia , Transtornos da Memória/patologia , Camundongos , Camundongos Transgênicos , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , FosforilaçãoRESUMO
BACKGROUND: Accumulation in the brain of small aggregates of amyloid beta-protein 42 (Abeta42) is the major pathogenic event of Alzheimer disease (AD). In familial early-onset AD this event is likely the result of Abeta42 overproduction; in the most common sporadic late-onset form of the disease the mechanisms of Abeta42 accumulation are unknown. METHODS: To address this issue the authors analyzed plasma levels of Abeta42 in 88 elderly patients with amnestic mild cognitive impairment (MCI), chosen as paradigm of preclinical sporadic AD. RESULTS: The authors found a significant increase of Abeta42 plasma levels in women with MCI, in comparison to the affected men and 72 cognitively normal age-matched subjects. The levels were independent of variables in education, apolipoprotein E genotype, cholesterol, and creatinine plasma concentrations, as well as hemoglobin content. CONCLUSIONS: The elevation of Abeta42 plasma levels in women with MCI may represent a biologic explanation for the sex-dependent increased incidence of late-onset AD in women identified by epidemiologic studies.
Assuntos
Peptídeos beta-Amiloides/sangue , Transtornos Cognitivos/sangue , Fragmentos de Peptídeos/sangue , Idade de Início , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologia , Apolipoproteínas E/genética , Biomarcadores , Colesterol/sangue , Transtornos Cognitivos/epidemiologia , Creatina/sangue , Escolaridade , Feminino , Hemoglobinas/análise , Humanos , Incidência , Masculino , Transtornos da Memória/sangue , Transtornos da Memória/epidemiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Distribuição por SexoAssuntos
Substituição de Aminoácidos , Demência/genética , Proteínas de Membrana/genética , Paraparesia Espástica/genética , Mutação Puntual , Adulto , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/biossíntese , Apolipoproteínas E/genética , Células Cultivadas , Meios de Cultivo Condicionados/química , Análise Mutacional de DNA , Demência/complicações , Demência/diagnóstico , Progressão da Doença , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Testes Neuropsicológicos , Paraparesia Espástica/complicações , Paraparesia Espástica/diagnóstico , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/biossíntese , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Presenilina-1RESUMO
BACKGROUND: Progressive supranuclear palsy (PSP) is characterized by a pure neurofibrillary tau pathology involving mainly basal ganglia and brainstem nuclei. In addition to a haplotype of the tau gene potentially favoring tau aggregation, lipoperoxidation has been shown to be associated with PSP tau pathology. OBJECTIVE: To analyze cdk5/p35 complex, a kinase that regulates neurite outgrowth, as a potential cellular mechanism underlying tau phosphorylation in brain tissues from PSP and control cases and comparatively in cerebral cortex from subjects with AD. METHODS: Cdk5/p35 protein levels and distribution were evaluated by immunoblotting and immunocytochemistry in brain regions from seven PSP, six AD, and seven control cases, with similar postmortem intervals. RESULTS: Total cdk5 protein levels were significantly increased by more than threefold in PSP tissue and were augmented in PSP neurons, codistributed with tau immunoreactivity. P35, the regulatory subunit of cdk5, was degraded by postmortem proteolysis to the same extent in PSP, AD, and control tissues. CONCLUSIONS: The proteolysis in vivo of p35, the regulatory subunit of the kinase, is not ascertainable because it is masked by its postmortem degradation. The study, however, indicates that in PSP, the alteration of cdk5 is different from that described in AD and suggests that the absence of amyloid beta protein deposition may account for the different pathways responsible for the same kinase activation.