Differential diagnosis of AD is still a challenge due to overlapping features with other
types of dementia. Biomarkers for the differential diagnosis of AD can improve the diagnostic value
of the disease and ensure an appropriate treatment of patients. The aim of this study was to evaluate
the potential of two neo-epitope fragments of Tau as serum biomarkers for differential diagnosis of
The neo-epitope fragments of Tau were assessed in a cross-sectional cohort of subjects with AD, MCI, other dementias or
subjects with non-dementia related memory complaints. The two Tau neo-epitope fragments were an ADAM10-generated
fragment (Tau-A) and a caspase-3-generated fragment (Tau-C). The serum levels of the fragments were measured by two
competitive ELISAs detecting Tau-A and Tau-C, respectively.
Tau-A and Tau-C were able to separate subjects with AD and MCI from those with other dementias (p < 0.0042 and p <
0.05), and Tau-A could also discriminate between AD and MCI patients and subjects with non-dementia related memory
complaints (p < 0.05). Tau-A showed a significantly greater discrimination between AD and MCI subjects and patients
with other dementias when compared to CSF biomarkers t-Tau and p-Tau. The ability of Tau-A to differentiate between
AD and MCI from other dementias was comparable with CSF Aβ1-42, t-Tau/Aβ1-42 and p-Tau/Aβ1-42. The separation between
the diagnostic groups was significantly improved when the CSF biomarkers as well as age and BMI were used in
combination with Tau-A (AUC = 0.87, 95% CI: 0.75-0.94) (p < 0.0001). In conclusion, this study shows that a neoepitope
fragment of Tau detected in serum can provide guidance on the differential diagnosis of AD.