The NIA-AA Research Framework [1] is an important advance in using biomarkers to define the AD spectrum. This approach will be useful in designing clinical trials and has an important role in characterizing the biomarker profile of participants entering trials. The Framework will assist in excluding Alzheimer spectrumparticipants from trials of non-Alzheimer dementias. The Framework facilitates considerations of target engagement and trial outcomes. The Framework effectively captures the current understanding of biomarkers of the Alzheimer’s spectrum using the ATN approach.
The eight types of ATN biomarker profiles include one with no abnormalities, four with amyloid changes (one with features of mixed dementia and one limited to amyloid changes characteristic of Alzheimer’s pathological changes without AD), and three with non-AD type profiles; most of the symptomatic forms comprise two types (A1T1N2; A1T1N1).
Mixed dementias and the complex neuropathology of AD are not addressed in the ATN Framework [13–15]. Characterizing trial participants with multiple biomarkers (e.g., specific levels of T and N in A1 individuals) may complicate recruitment while improving the biological definition of the trial population. The imperfect relationships between the two amyloid, two tau, and three neurodegeneration markers may contribute to trial population heterogeneity, and the less-than-complete correlations between biomarkers and brain pathology challenge researchers to refine the Framework. Finally, the limited correlation of cognitive decline with ATN biomarker changes demonstrates that factors outside this repertoire are likely contributing to the cognitive impairment. Biomarkers of these other pathologies and treatments to address them may play an important role in the quest to find DMTs for those with or at risk for AD. The NIA-AA Framework is a key advance in establishing a clinically viable biologically defined characterization of the Alzheimer’s spectrum with application to clinical trials.
翻譯：
NIA-AA研究框架是使用生物標記來定義AD疾病譜的重要進展。
這種方法在設計臨床試驗時非常有用，並且在表徵參與試驗的參與者的生物標誌物特徵方面具有關鍵作用。該框架將有助於將阿爾茨海默氏症的參與者排除在非阿爾茨海默病痴呆症的試驗之外。
該框架有助於招募目標人群參與臨床試驗。
該框架使用ATN方法有效地捕獲了當前對阿爾茨海默病的生物標誌物的理解。八種類型的ATN生物標誌物分析包括一種沒有異常，一種具有澱粉樣蛋白變化（一種具有混合性痴呆的特徵，一種僅限於阿爾茨海默氏症無AD的病理變化的澱粉樣變化），三種具有非AD型特徵;大多數症狀形式包括兩種類型（A1T1N2; A1T1N1）。
混合性痴呆和AD的複雜神經病理學在ATN框架中沒有涉及。用多種生物標誌物（例如，A1個體中特定水平的T和N）表徵試驗參與者可能使招募複雜化，同時改善試驗群體的生物學定義。
兩種澱粉樣蛋白，兩種tau蛋白和三種神經變性標記物之間的不完善關係可能有助於試驗群體的異質性，生物標誌物與腦病理學之間的不完全相關性挑戰研究人員重新構建框架。
認知衰退與ATN生物標誌物變化的有限相關性表明，該曲目之外的因素也有可能導致認知障礙。解決這些疾病的其他病理和治療方法的生物標誌物可能在尋找有AD或有AD風險的DMT的過程中發揮重要作用。
因此，NIA-AA框架是建立臨床可行的生物學定義阿爾茨海默疾病譜的臨床試驗的關鍵進展。
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關鍵字: AA 標誌物 biomarkers
