γ-Secretase Activity Is Associated with Braak Senile Plaque Stages.
Am J Pathol
; 190(6): 1323-1331, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32201261
ABSTRACT
Amyloid ß-proteins (Aßs) Aß1-42 and Aß1-43 are converted via two product lines of γ-secretase to Aß1-38 and Aß1-40. This parallel stepwise processing model of γ-secretase predicts that Aß1-42 and Aß1-43, and Aß1-38 and Aß1-40 are proportional to each other, respectively. To obtain further insight into the mechanisms of parenchymal Aß deposition, these four Aß species were quantified in insoluble fractions of human brains (Brodmann areas 9 to 11) at various Braak senile plaque (SP) stages, using specific enzyme-linked immunosorbent assays. With advancing SP stages, the amounts of deposited Aß1-43 in the brain increased proportionally to those of Aß1-42. Similarly, the amounts of deposited Aß1-38 correlated with those of Aß1-40. Surprisingly, the ratios of deposited Aß1-38/Aß1-42 and Aß1-40/Aß1-43 were proportional and discriminated the Braak SP stages accurately. This result indicates that the generation of Aß1-38 and Aß1-40 decreased and the generation of Aß1-42 and Aß1-43 increased with advancing SP stages. Thus, Aßs deposition might depend on γ-secretase activity, as it does in the cerebrospinal fluid. Here, the extracted γ-secretase from Alzheimer disease brains generates an amount of Aß1-42 and Aß1-43 compared with cognitively normal brains. This refractory γ-secretase localized in detergent-solubilized fractions from brain cortices. But activity modulated γ-secretase, which decreases Aß1-42 and Aß1-43 in the cerebrospinal fluid, localized in detergent-insoluble fractions. These drastic alterations reflect Aß situation in Alzheimer disease brains.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Placa Amiloide
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Secretases da Proteína Precursora do Amiloide
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article