The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome.
Neuropathol Appl Neurobiol
; 44(3): 314-327, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-28455903
ABSTRACT
AIMS:
Down syndrome (DS) is a common cause of mental retardation accompanied by cognitive impairment. Comprehensive studies suggested a link between development and ageing, as nearly all individuals with DS develop Alzheimer disease (AD)-like pathology. However, there is still a paucity of data on tau in early DS to support this notion.METHODS:
Using morphometric immunohistochemistry we compared tau phosphorylation in normal brains and in brains of individuals with DS from early development until early postnatal life.RESULTS:
We observed in DS a critical loss of physiological phosphorylation of tau. Rhombencephalic structures showed prominent differences between controls and DS using antibodies AT8 (Ser-202/Thr-205) and AT180 (Thr-231). In contrast, in the subiculum only a small portion of controls deviated from DS using antibodies AT100 (Thr-212/Ser-214) and AT270 (Thr-181). With exception of the subiculum, phosphorylation-independent tau did not differ between groups, as confirmed by immunostaining for the HT-7 antibody (epitope between 159 and 163 of the human tau) as well.DISCUSSION:
Our observations suggest functional tau disturbance in DS brains during development, rather than axonal loss. This supports the role of tau as a further important player in the pathophysiology of cognitive impairment in DS and related AD.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
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Proteínas tau
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Síndrome de Down
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Feto
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Neuropathol Appl Neurobiol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Austria