알쯔하이머병 환자 뇌의 해마피질내 rab6 단백의 발현 = Immunohistochemical Study on GTP-binding Rab6 Expression in the Hippocampal Cortices of the Alzheimer Brain

국문 초록 (Abstract)

베타 아밀로이드는 아밀로이드 전구단백이 β-secretase 및 γ-secretase에 의하여 분해됨으로써 생성된 후 세포 밖으로 배출되어 뇌의 다양한 부위에 축적되어 신경세포 독성을 나타내므로 알쯔하이머병의 주요한 원인 물질 중 하나로 인식되고 있다. GTP 결합 단백질인 rab 단백은 물질이동에 다양한 역할을 수행하며, 특히 rab6 단백은 골지복합체에서 형질내세망으로 물질의 역전달에 관여하는 것으로 추정되고 있다. 아밀로이드 전구단백이 rab6 단백에 의해 역전달되어 이동될 경우 골지복합체에 존재하는 β-secretase와 형질내세망에 존재하는 γ-secretase의 순차적인 작용에 의하여 베타 아밀로이드의 생성이 증가될 가능성이 있다. 그러므로 본 연구에서는 알쯔하이머병의 병리학적 병기에 따른 신경세포내 rab6 단백의 활성 변동을 조사하여 베타 아밀로이드 생성과 rab6 단백 활성의 연관성에 대한 기초자료를 얻기 위하여 이 연구를 시도하였다.
연구에 사용된 알쯔하이머 뇌는 손상 정도에 따라 임상전기와 임상기로 분류한 후 인지기능과 밀접한 관련이 있는 해마피질에서 질병의 경과에 따른 rab6 단백의 발현여부를 관찰하고자 항rab6 단백 항체를 이용한 면역 조직화학적 염색을 시행하였다.
결과를 종합하면, 알쯔하이머병의 특징적 병리소견인 베타 아밀로이드는 관통경로를 따라 치아이랑의 분자층에서 다수 관찰되었고, 알쯔하이머병이 진행될수록 해마피질내 모든 구획의 피라밋세포에서 rab6 단백의 발현이 증가되었다. 알쯔하이머 뇌의 해마피질내 CA1 및 CA3 구획이 CA2 구획에 비해 rab6 단백의 발현이 증가되었으며 이는 내후각뇌피질에서 치아이랑의 분자층을 경유하여 CA3 구획에 도달한 후 다시 CA1 구획으로 투사되는 기억회로의 관통경로 손상과 밀접한 관계가 있을 것으로 생각된다.

다국어 초록 (Multilingual Abstract)

The ras-related GTP binding protein, rab6, is located in late Golgi compartment. Modulation of β-and γ-secretase activity may lead to production of β-amyloid fragments that are ultimately deposited in senile plaques at the brain of Alzheimer patients. Because modulation of rab6-mediated intracellular transport has been known to affect amyloid precursor protein (APP) processing, we investigated the rab6 immunoreactivity on the hippocampal neurons in the Alzheimer brains, according to the pathological staging of the disease.
A total of 30 brains were used for this study. Campbell’s silver stain for β-amyloid and immunohistochemistry for rab6 protein were employed. The cortices of the hippocampal formation and the neighboring temporal neocortex were observed.
The results are obtained as follows:
1. In normal elderly brains, no amyloid plaque is seen. In Alzheimer brains, a number of amyloid plaques are seen at the temporal neocortex and dentate gyrus.
2. In normal elderly brains, the perikaria of the pyramidal cells at the CA1 sector shows weak rab6 immunoreactivity.
At the CA2 and CA3 sectors, trace immunoreactivity is observed in the pyramidal cells.
3. In preclinical Alzheimer brains, the perikaria of the pyramidal cells at the CA1 sector shows moderate rab6
immunoreactivity and the cells at the CA2 sector show weak immunoreactivity. A weak to moderate immunoreactivity
is seen in the pyramidal cells of the CA3 sector.
4. In clinical Alzheimer brains, the pyramidal cells at the CA1 and CA3 sectors show strong rab6 immunoreactivity, but the cells at the CA2 sector shows moderate immunoreactivity.
It is suggested that alteration of intracellular protein transport caused by abnormal rab6 activity may modulate
amyloid precursor protein processing, which results in β-amyloid production.

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