TY - JOUR
T1 - The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome
AU - Milenkovic, I.
AU - Jarc, J.
AU - Dassler, E.
AU - Aronica, E.
AU - Iyer, A.
AU - Adle-Biassette, H.
AU - Scharrer, A.
AU - Reischer, T.
AU - Hainfellner, J. A.
AU - Kovacs, G. G.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85019893072&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/28455903
U2 - https://doi.org/10.1111/nan.12406
DO - https://doi.org/10.1111/nan.12406
M3 - Article
C2 - 28455903
SN - 0305-1846
VL - 44
SP - 314
EP - 327
JO - Neuropathology and applied neurobiology
JF - Neuropathology and applied neurobiology
IS - 3
ER -