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

I. Milenkovic, J. Jarc, E. Dassler, E. Aronica, A. Iyer, H. Adle-Biassette, A. Scharrer, T. Reischer, J. A. Hainfellner, G. G. Kovacs

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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.
Original languageEnglish
Pages (from-to)314-327
JournalNeuropathology and Applied Neurobiology
Volume44
Issue number3
DOIs
Publication statusPublished - 2018
Externally publishedYes

Cite this

Milenkovic, I., Jarc, J., Dassler, E., Aronica, E., Iyer, A., Adle-Biassette, H., ... Kovacs, G. G. (2018). The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome. Neuropathology and Applied Neurobiology, 44(3), 314-327. https://doi.org/10.1111/nan.12406