Altered p59Fyn kinase expression accompanies disease progression in Alzheimer's disease: implications for its functional role.
Alzheimer's disease (AD) is characterized by progressive decline in memory and other cognitive domains, accompanied by early loss of presynaptic terminals, amyloid-bearing neuritic plaques and neurofibrillary tangles containing hyperphosphorylated tau. The mechanisms leading to neurodegeneration are not completely understood, however, recent evidence suggests that alterations in p59Fyn kinase, an Src family tyrosine kinase, might contribute to AD pathogenesis. In this context, the main objective of the present study was to investigate the relationship between Fyn protein levels and the neurological and neuropathological alterations in AD. We found, by quantitative immunoblotting, that in AD, Fyn levels were increased in the insoluble fraction and decreased in the soluble fraction. Soluble Fyn levels were directly correlated with the cognitive scores and levels of synaptophysin immunoreactivity, and inversely correlated with neurofibrillary tangle counts in the frontal cortex. Consistent with these findings, the immunocytochemical analysis showed that in AD cases, Fyn levels were decreased in the synapses and increased in the neuronal cell bodies where it was colocalized with neurofibrillary tangles. Taken together, these findings suggest that alterations in Fyn localization might be associated with neurofibrillary pathology and synapse loss in AD.
Ho
Gilbert J
GJ
Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA.
Hashimoto
Makoto
M
Adame
Anthony
A
Izu
Matthew
M
Alford
Michael F
MF
Thal
Leon J
LJ
Hansen
Lawrence A
LA
Masliah
Eliezer
E
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016014:Linear Models; D008609:Mental Status Schedule / Q000706:statistics & numerical data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism; D011180:Postmortem Changes; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D018709:Statistics, Nonparametric; D013347:Subcellular Fractions / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins
C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D016708:Synaptophysin; D016875:tau Proteins; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases