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Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death markers across the Alzheimer's disease Braak stages: a quantitative study in humans.
Theofilas, Panos; Ehrenberg, Alexander J; Nguy, Austin; Thackrey, Julia M; Dunlop, Sara; Mejia, Maria B; Alho, Ana T; Paraizo Leite, Renata Elaine; Rodriguez, Roberta Diehl; Suemoto, Claudia K; Nascimento, Camila F; Chin, Marcus; Medina-Cleghorn, Daniel; Cuervo, Ana Maria; Arkin, Michelle; Seeley, William W; Miller, Bruce L; Nitrini, Ricardo; Pasqualucci, Carlos Augusto; Filho, Wilson Jacob; Rueb, Udo; Neuhaus, John; Heinsen, Helmut; Grinberg, Lea T.
Afiliação
  • Theofilas P; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Ehrenberg AJ; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Nguy A; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Thackrey JM; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Dunlop S; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Mejia MB; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Alho AT; Hospital Albert Einstein, São Paulo, Brazil; Department of Pathology, LIM-22, University of São Paulo Medical School, São Paulo, Brazil.
  • Paraizo Leite RE; Division of Geriatrics, LIM-22, University of São Paulo Medical School, São Paulo, Brazil.
  • Rodriguez RD; Department of Pathology, LIM-22, University of São Paulo Medical School, São Paulo, Brazil.
  • Suemoto CK; Division of Geriatrics, LIM-22, University of São Paulo Medical School, São Paulo, Brazil.
  • Nascimento CF; Department of Pathology, LIM-22, University of São Paulo Medical School, São Paulo, Brazil.
  • Chin M; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
  • Medina-Cleghorn D; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
  • Cuervo AM; Departments of Developmental and Molecular Biology, Anatomy and Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Arkin M; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
  • Seeley WW; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Miller BL; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Nitrini R; Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil.
  • Pasqualucci CA; Department of Pathology, LIM-22, University of São Paulo Medical School, São Paulo, Brazil.
  • Filho WJ; Division of Geriatrics, LIM-22, University of São Paulo Medical School, São Paulo, Brazil.
  • Rueb U; Dr. Senckenbergisches Chronomedizinisches Institut, Department of Anatomy, J. W. Goethe University Frankfurt am Main, Frankfurt, Germany.
  • Neuhaus J; Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
  • Heinsen H; Department of Pathology, LIM-22, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Wuerzburg, Wuerzburg, Germany.
  • Grinberg LT; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, LIM-22, University of São Paulo Medical School, São Paulo, Brazil. Electronic address: lea.grinberg@ucsf.edu.
Neurobiol Aging ; 61: 1-12, 2018 01.
Article em En | MEDLINE | ID: mdl-29031088
Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation. We fit linear regressions with each count as outcomes, with Braak score and age as the predictors. In progressive Braak stages, intraneuronal active caspase-6 positivity increases both alone and overlapping with NFTs. Likewise, the proportion of NFT-bearing neurons showing autophagosomes increases. Overall, caspases may be involved in upstream cascades in AD and are associated with higher NFTs. Macroautophagy changes correlate with increasing NFT burden from early AD stages.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Emaranhados Neurofibrilares / Morte Celular / Doença de Alzheimer / Neurônios Tipo de estudo: Prognostic_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Emaranhados Neurofibrilares / Morte Celular / Doença de Alzheimer / Neurônios Tipo de estudo: Prognostic_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article