2 research outputs found
Isoformāspecific upregulation of FynT kinase expression is associated with tauopathy and glial activation in Alzheimerās disease and Lewy body dementias
This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordāÆCumulative data suggest the involvement of Fyn tyrosine kinase in progression of
Alzheimer's disease (AD). Previously, our group has shown increased
immunoreactivities of the FynT isoform in AD neocortex (with no change in the
alternatively spliced FynB isoform) which associated with neurofibrillary
degeneration and reactive astrogliosis. Since both the aforementioned
neuropathological features are also frequently found in Lewy Body dementias (LBD),
we investigated potential perturbations of Fyn expression in the postmortem
neocortex of patients with AD, as well as those having one of the two main
subgroups of LBD: Parkinsonās disease dementia (PDD) and dementia with Lewy
bodies (DLB). We found selective upregulation of FynT expression in AD, PDD and
DLB which also correlated with cognitive impairment. Furthermore, increased FynT
expression correlated with hallmark neuropathological lesions, soluble Ī²-amyloid
and phosphorylated tau, as well as markers of microglia and astrocyte activation. In
line with the human postmortem studies, cortical FynT expression in aged mice
transgenic for human P301S tau was upregulated and correlated with accumulation
of aggregated phosphorylated tau as well as with microglial and astrocytic markers.
Our findings point to FynT being an important mediator of disease progression in
neurodegenerative dementias, likely via effects on tauopathy and
neuroinflammation.National Medical Research Council, Singapor