2025 Volume 42 Issue 2 Pages 72-78
With the advent of disease modifying therapies for Alzheimer disease (AD) being used in clinical practice, biomarkers that can accurately diagnose the neuropathology of AD and other dementing disorders have become essential. The definitive diagnosis of brain amyloid and tau pathologies is now possible through PET imaging, and there is a growing demand for blood–based biomarkers suitable for screening tests. In 2018, the ATN classification system was proposed and ATN biomarkers have been introduced for the diagnosis and staging for AD. However, all the ATN biomarkers proposed in 2018 were cerebrospinal fluid (CSF) biomarkers. Since 2018, considerable progress has been made in the field of research on biomarkers for AD. Under such circumstances, the “Revised Criteria for Diagnosis and Staging of AD” has been presented by the Alzheimer's Association Workgroup in 2024. The biggest difference of the biomarkers featured in 2024 criteria from those in 2018 is that CSF or plasma p–tau217 and 181 are not any more classified as the biomarkers for tau proteinopathy, but classified as the biomarkers for brain amyloid in the same category as Amyloid–PET. Therefore, we now need a fluid “T” biomarker that reflects brain tau burden without interference from brain amyloid. We thus developed a novel plasma T–BM, mid–p–tau, in QST and have shown that the plasma mid–p–tau levels showed linear correlations with the tau PET accumulation in the Braak 3&4 and 5&6 regions. We concluded that our novel plasma mid–pTau assay serves as a promising surrogate biomarker for AD–tau deposition, which facilitates efficient and accurate selection the patients suitable for anti–amyloid therapies. Furthermore, it will be necessary from now on to establish multiple biomarkers, including those beyond ATN, and apply them to clinical practice.
