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Wiley, Neuropathology and Applied Neurobiology

DOI: 10.1111/nan.12406

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The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Data provided by SHERPA/RoMEO

Abstract

AimsDown 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.MethodsUsing morphometric immunohistochemistry we compared tau phosphorylation in normal brains and in brains of individuals with DS from early development until early postnatal life.ResultsWe 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.DiscussionOur 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.