2013-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/685436摘要：背景: 近年來失智症生物標記進展提供了在阿茲海默症的早期甚至臨床前診斷的可能性，讓我們在阿茲海默症的早期病理變化剛出現時便開始治療。腦脊髓液中的 Aβ42蛋白濃度的下降與 tau蛋白的上升是目前認為診斷阿茲海默症較為可靠的生物標記。但其他組織液的 Aβ42蛋白與 tau蛋白濃度的上升或下降則尚無定論。此外與類澱粉相關之失智症並非只有輕度知能障礙或者阿茲海默症而已，在有些巴金森失智症，路易氏體失智症，額顳葉型失智症和健康老年人身上都有可能存在 。 研究方法：利用血漿中的生物標記、結構性磁振造影、類澱粉射出斷層造影、去氧氟-18葡萄糖射出斷層造影進行縱貫性演變。我們將使用免疫減磁法來量測血漿中 Aβ40和 Aβ42，以及 tau蛋白濃度。研究對象包括 15名輕度知能障礙患者，15名阿茲海默症，10名巴金森失智症，10名路易氏體失智症，10名原發性進行性失語症之額顳葉型失智症和 20名健康老年人。所有受試都接受相同的神經心裡學檢查來評估記憶、注意力、執行功能、視覺空間功能。我們並將在 18個月之後進行如上所述包括神經心理、血漿生化、神經影像與神經心裡學測驗之所有檢查。 預期結果與結論：可得到不同生物標記在各種類澱粉相關之失智症的量化與大腦分佈類型與及隨著時間的演變狀態。<br> Abstract: Background: Recent advance in biomarkers provides possible early or preclinical diagnosis of (Alzheimer’s disease) AD which implements treating patients at early Alzheimer's pathology. Decreased Aβ42 and increased tau proteins in CSF are considered reliable biomarkers for AD while the issue of plasma tau and amyloid proteins remains unsolved. However, amyloid related dementias can be found not only in AD or mild cognitive impairments but also in some patients with Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), Primary progressive aphasia (PPA) of frontal temporal lobe dementia (FTLD) and healthy elderly. Methods: We aimed to investigate the potential of using plasma biomarkers, structure MRI, PiB-PET and FDG-PET for AD and to explore the longitudinal evolution and relation to neuroimaging and neuropsychological test. We will use immunomagnetic reduction assay to measure amyloid Aβ40, Aβ42 and tau proteins in 15 subjects with MCI, 15 with early AD, 10 with PDD, 10 with DLB, PPA of FTLD and 20 controls. All subjects will receive a 3D MRI and a DTI study, and will receive a same set of neuropsychological tests assessing memory, executive, attention and visuospatial functions. All subjects will also be invited to receive PiB- and FDG PET scans after detailed explanation of the radiation exposure. We will follow up all participants with an interval of about 18 months including all the aforementioned biochemical, neuroimaging and neuropsycological studies. Expected results will include the following aspects from both the cross-sectional and longitudinal studies. From the cross-sectional study we can observe the cut-off levels of plasma biomarkers, patterns of brain atrophy and amyloid depositions of different type of amyloid related dementias. From the longitudinal study of the biomarkers on various amyloid related dementias we will be able to observe the evolution of the plasma biomarkers, brain structure and amyloid deposition of the brain throughout the time. Conclusion: In our previous studies we found that plasma amyloids and tau proteins are useful biomarkers for MCI and AD. However we need to know about the evolution of the plasma biomarkers throughout the time by longitudinal studies. Also patterns of amyloid deposition in the brain and quantitative patterns of evolution throughout the time should be explored in various amyloid related dementias.