| Summary: | 碩士 === 國立成功大學 === 細胞生物及解剖學研究所 === 91 === The major pathological hallmarks of Alzheimer’s disease (AD)
are neurofibrillary tangles and senile plaques. Accumulation and
depositions of beta amyloid (Ab) peptides in brain were proposed to
play seminal roles in the pathogenesis of AD. However, the
mechanism of Ab aggregation in brain remains obscure. The
objective of this study is to search for region-specific proteins that
participate in Ab aggregation. AD parietal lobe gray and white
matter and cerebellum were homogenized, and the supernatants were
immunoprecipitated against Ab. Electrophoresis and silver stain
revealed a major band at 14~16 KD associated with exogenous
administrated Ab. LC/MS/MS identified three potential Ab binding
proteins, alpha synuclein, hemoglobin alpha and beta chains.
Because two of three candidates were the components of
hemoglobin (Hb), the Hb concentration in different brain regions and
its ability to interact with Ab were examined. Western blot analysis
showed that parietal lobe gray matter had higher Hb levels than
those of parietal white matter, and which in turn was higher than
those of cerebellum. These results are parallel with the AD brain Ab
pahtalogies. Furthermore, Hb was shown to prevent Ab aggregation
in time and dose-dependent manners. Finally, immunohistochemical
evidences confirmed the co-localization of Hb with senile plaques,
especially in cores. Taken together these results suggest that Hb is
associated with Ab in AD brain and may involved in Ab aggregation.
|
|---|
