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작성일 : 19-12-04 17:42
알츠하이머병
 글쓴이 : 녹원명문한…
조회 : 5,693  

알츠하이머병은 치매를 일으키는 가장 흔한 퇴행성 뇌질환으로 서서히 발병하여 기억력을 포함한 인지기능의 악화가 점진적으로 진행되는 병으로, 치매의 원인 중 60-70%를 차지합니다.

알츠하이머는 대뇌피질과 몇몇 피질하 영역에서 뉴런과 시냅스의 소실을 특징으로 하며, 측두엽과 두정엽, 전두엽과 대상회(cingulate gyrus)의 일부의 퇴행을 포함하여 관련된 부위의 전반적인 위축이 발생합니다. 아래 그림은 정상측에 비해 위축되어 보이는 알츠하이머병 뇌를 표현한 그림입니다. 이러한 위축은 MRI와 PET을 이용하여 확인할 수 있습니다.

 

그림3.jpg


현미경으로 알츠하이머병 환자의 뇌 조직을 검사하였을 때 특징적인 병변인 신경반(neuritic plaque)과 신경섬유다발(neurofibrillary tangle) 등이 관찰되고, 육안 관찰 시에는 신경세포 소실로 인해 전반적 뇌 위축 소견이 보입니다. 이러한 뇌 병리 소견은 질병 초기에는 주로 기억력을 담당하는 주요 뇌 부위인 해마와 내후각뇌피질 부위에 국한되어 나타나지만 점차 두정엽, 전두엽 등을 거쳐 뇌 전체로 퍼져나갑니다. 알츠하이머병의 정확한 발병 기전과 원인에 대해서는 정확히 알려져 있지는 않습니다.


현재 베타 아밀로이드(beta-amyloid)라는 작은 단백질이 과도하게 만들어져 뇌에 침착되면서 뇌 세포에 유해한 영향을 주는 것이 발병의 핵심 기전으로 알려져 있으나, 그 외에도 뇌 세포의 골격 유지에 중요한 역할을 하는 타우 단백질(tau protein)의 과인산화, 염증반응, 산화적 손상 등도 뇌 세포 손상에 기여하여 발병에 영향을 미치는 것으로 보입니다. 사진에서 알츠하이머의 대표적인 병리적 소견인 senile plaque와 neurofibrillary tangle이 관찰되는데,  신경반(혹은 노인반)은 베타 아밀로이드 단백질의 침착과 관련되며, 신경섬유다발은 타우 단백질 과인산화와 연관이 있습니다.


이러한 뇌 병리 침범 부위의 진행에 따라 초기에는 기억력 저하가 주로 나타나다가 진행됨에 따라 점진적인 경과를 보이면서 임상 증상이 다양해지고 점점 더 심해지게 되는 것입니다.


 

그림4.png

Skaper SD. Alzheimer's disease and amyloid: culprit or coincidence? Int Rev Neurobiol. 2012;102:277-316.


알츠하이머병의 생화학적 기전에 대해서 살펴보겠습니다.

알츠하이머병은 베타 아밀로이드와 타우 단백질이 비정상적으로 결합하여 축적되는 질환인데,
먼저 베타 아밀로이드를 보면 베타 아밀로이드는 APP라고 불리는 amyloid precursor protein에서 떨어져 나온 fragment인데, APP는 뉴런의 membrane을 관통하는 transmembrane protein으로서, 뉴런의 성장과 생존, 손상 후 회복에 중요한 역할을 합니다.

알츠하이머병에서는 γ-secretase와 β-secretase가 APP를 작은 조각들로 분해하고, 그 중 일부가 amyloid beta이고, 그것들이 모여 뉴런 밖에 쌓이게 되는데, 그것이 senile plaque로 보이는 것입니다.

 

그림5.jpg


다음으로 tau 단백질에 대해 살펴보겠습니다.
알츠하이머는 타우 단백질의 비정상적 집적으로도 발생합니다.
모든 뉴런들은 microtubule로 이루어진 cytoskeleton(세포골격)을 가지고 있는데, microtubule은 track과 같은 역할을 해서, 뉴런의 transport 시스템을 관장합니다. 타우 단백질은 인산화되었을 때 이러한 microtubule을 안정화시키지만, 화학적 변화를 통해 과인산화 되게 되면 타우 섬유끼리 짝을 이루기 시작하고, 점차 신경섬유 다발을 만들어 뉴런의 transport 시스템을 붕괴시킵니다.


 

그림6.jpg


그림7.jpg

https://en.wikipedia.org/wiki/Alzheimer%27s_disease


 

그림8.jpg

http://science.sciencemag.org.openlink.khu.ac.kr:8080/content/358/6359/45/tab-figures-data


이러한 베타 아밀로이드와 타우 단백질을 겨낭한 다양한 치료법들이 시도되고 있지만,
알츠하이머병의 진행을 막기에는 역부족인 상황입니다.


한약(육미지황탕가감 등)을 이용하여 알츠하이머병에 효과를 본 다양한 연구결과들이 최근에 발표되고 있는데요.

환자분의 상태, 즉 변증에 맞는 한약 처방과 침치료 등의 한의학적 치료가 알츠하이머병의 진행을 늦추고, 환자분의 제반 컨디션을 향상시키는데 도움이 될 수 있습니다.


Maria 23-02-14 07:37
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Barbara 23-03-13 04:42
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Joseph 23-04-25 20:03
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Lisa 23-05-12 19:01
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