Premium
[O2–02–06]: ALZHEIMER‐LIKE PATHOPHYSIOLOGICAL CHANGES IN THE NON‐DEMENTED DOWN SYNDROME POPULATION
Author(s) -
Lao Patrick J.,
Handen Benjamin L.,
Betthauser Tobey J.,
Price Julie C.,
Klunk Bill E.,
Bulova Peter D.,
Hartley Sigan L.,
Tumuluru Rameshwari V.,
Murali Dhanabalan,
Mathis Chester,
Cohen Ann D.,
Barnhart Todd E.,
Tudorascu Dana L.,
Devenny Darlynne,
Johnson Sterling C.,
Christian Brad T.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.07.154
Subject(s) - pittsburgh compound b , population , atrophy , nuclear medicine , pathology , medicine , standardized uptake value , statistical parametric mapping , alzheimer's disease , psychology , cardiology , positron emission tomography , magnetic resonance imaging , disease , radiology , environmental health
the activity. In AD brain, GSK-3b is truncated at the C-terminus by over-activated calpain I, leading to an increase in its activity. However, the effect of truncation on its phosphorylation is unknown.Methods:We determined themolecular mechanism bywhich the truncation of GSK3b leads to increase in its activity by usingWestern blots, immunofluorescencent staining, subcellular fractionation, in vitro dephosphorylation, and co-immunoprecipitation. Results:We found that in AD brain and in cultured cells, theC-terminally truncatedGSK-3bwas less phosphorylated at Ser9 than the full-length enzyme. The truncated GSK-3b was observed more than the full-length in the nucleus in cultured cells and in AD brain. The truncated GSK-3b interacted with protein phosphatase 2A (PP2A) more strongly and was dephosphorylated by PP2A more efficiently than the full-lengthGSK-3b.Conclusions:TheC-terminal truncation of GSK-3b promotes its nuclear translocation and enhances its interaction with and dephosphorylation by PP2A. Thus, the truncation of GSK-3b may enhance its activity through Ser9 dephosphorylation by PP2A. These findings shed a new light onto the role of calpain-GSK-3b-PP2A in tau pathogenesis in AD.