The Compartmentalization of Amyloid-ß in Idiopathic Normal Pressure Hydrocephalus Brain Biopsies.
J Alzheimers Dis
; 99(2): 729-737, 2024.
Article
em En
| MEDLINE
| ID: mdl-38669551
ABSTRACT
Background:
Amyloid-ß (Aß) is one of the hallmark lesions of Alzheimer's disease (AD). During the disease process, Aß undergoes biochemical changes, producing toxic Aß variants, proposed to be detected within the neurons. Idiopathic normal pressure hydrocephalus (iNPH) causes cognitive impairment, gait, and urinary symptoms in elderly, that can be reversed by a ventriculo-peritoneal shunt. Majority of iNPH subjects display different Aß variants in their brain biopsies, obtained during shunting.Objective:
To study the cellular compartmentalization of different Aß variants in brain biopsies from iNPH subjects.Methods:
We studied the cellular localization of different proteoforms of Aß using antibodies towards different amino acid sequences or post-translational modifications of Aß, including clones 4G8, 6F/3D, unmodified- (7H3D6), pyroglutamylated- (N3pE), phosphorylated-(1E4E11) Aß and Aß protein precursor (AßPP), in brain biopsies from 3 iNPH subjects, using immunohistochemistry and light microscopy (LM), light microscopy on semi-thin sections (LMst), and electron microscopy (EM).Results:
In LM all Aß variants were detected. In LMst and EM, the Aß 4G8, 6F/3D, and the pyroglutamylated Aß were detected. The AßPP was visualized by all methods. The Aß labelling was located extracellularly with no specific signal within the intracellular compartment, whereas the AßPP was seen both intra- and extracellularly.Conclusions:
The Aß markers displayed extracellular localization when visualized by three assessment techniques, reflecting the pathological extracellular accumulation of Aß in the human brain. No intracellular Aß pathology was seen. AßPP was visualized in intra- and extracellularly, which corresponds to the localization of the protein in the membranes of cells and organelles.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Peptídeos beta-Amiloides
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Hidrocefalia de Pressão Normal
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article