As discussed above, the jointly proposed NIA-AA Research Framework calls for a biological definition of AD with emphasis on categorizing AD pathology based on measurement of specific biomarkers including Aβ, Tau, neurodegeneration, and cognitive symptoms (Jack et al., 2018). In this framework, specific combinations of individual measures have different interpretations. Presence of Aβ biomarkers (e.g., the Aβ 42/40 ratio) determines presence on the Alzheimer’s continuum (Table 2). Pathologic tau biomarkers (e.g., pTau) can indicate non-AD pathology if detected in isolation; however, combined Aβ and Tau biomarkers indicates presence of AD because both are required for diagnosis of the disease. The addition of cognitive symptoms is also used for disease staging with dementia (e.g., cognitive impairment in several domains with additional behavioral symptoms) indicating the most severe stage (Jack et al., 2018). In this study, we took a translational approach and evaluated AD biomarkers within specific brain regions of the 3xTg-AD mice and evaluated the results in the context of the NIA-AA framework.
