Selective upregulation of FynT tyrosine kinase in neurodegenerative dementia correlates well with tau pathology and neuroinflammation: Human neuropathology/clinico‐pathologic correlations

Background Fyn tyrosine kinase is involved in the disease progression of Alzheimer’s disease (AD). Our lab has previously reported an isoform‐specific role of FynT tyrosine kinase in AD brain which is associated with neurodegeneration and reactive astrogliosis [Lee et al., 2016]. In view of AD‐related neuropathology and neuroinflammation were not exclusively found in AD, the objective of the study is to investigate whether differential alternative splicing of Fyn to favour FynT expression could also be detected in other neurodegenerative dementias including dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Method Post‐mortem human brain tissues (prefrontal cortex Brodmann area 9 (BA9) and temporal cortex (BA21) derived from subjects diagnosed with AD, DLB, PDD, as well as controls (CTRL) without neurological or psychiatric diseases were provided by the Brains for Dementia Research (BDR). The brain tissues were recorded for Mini‐Mental State Examination (MMSE) and Braak staging. The brain tissues were processed accordingly for ELISA, real‐time PCR, capillary electrophoresis and HTA array studies. Result Selective and significant up‐regulation of FynT isoform expression in prefrontal and temporal cortex of AD, DLB and PDD when compared with CTRL was observed to significantly correlate with cognitive impairment and neuropathological characteristics. FynT induction in AD, DLB and PDD was associated with neuroinflammatory markers. Synaptic dysfunction could be the adverse impacts of FynT induction in neurodegenerative dementias. Conclusion Using an independent cohort, we reported that FynT induction was not exclusive to AD, but also detected in neurodegenerative dementia including DLB and PDD. FynT induction was closely associated with tau pathology and neuroinflammation, which likely contributed to synaptic dysfunction and cognitive impairment. Potential therapeutic treatment should specifically target the disease‐associated isoform of Fyn.