Low CSF amyloid-β (Aβ1–42 or Aβ42/40 ratio) are biomarkers of Alzheimer's disease (AD), especially combined with high total Tau (T-Tau) and hyperphosphorylated Tau (P-Tau). To test the relation of lowering of amyloid-β42 and T-Tau and P-Tau release in CSF, we analyzed in healthy elderly and MCI the relationship of amyloid status towards T-Tau and P-Tau. Baseline CSF of 253 subjects with a CDR score of 0 or 0.5 was analyzed for Aβ1–42 (INNOTEST®β-amyloid1–42), Aβ42/40 ratio (MSD V-Plex), T-Tau and P-Tau (INNO-BIA AlzBio3). Amyloid positivity was identified via low CSF Aβ1–42 (< 600 ng/L) and Aβ42/40*10 ratio (< 0.89). Pearson correlation and linear regression were used to compare levels. In the overall sample, we found a moderate inverse correlation between T-Tau and P-Tau and Aβ1–42 (R = -0.42 and -0.38, P < 0.0001) or the Aβ42/40 Ratio (R= -0.54 and -0.56, P < 0.0001). While in amyloid positive subjects the Aβ42/40 ratio similarly correlated inversely with T-Tau (R = -0.37, P < 0.001) and P-Tau (r=-0.41, P < 0.0001), there was no correlation with Aβ1–42. The reverse was observed in amyloid negative subjects where Aβ1–42 positively correlated with T-Tau (R = 0.38, P < 0.001) and P-Tau (R = 0.36, P < 0.001), while the Aβ42/40 ratio did not correlate. Aβ40 positively correlated with T-Tau (R=0.59 and R=0.82, P < 0.0001) or P-Tau (R=0.68, P < 0.0001 and R 0.57, P < 0.001) in both amyloid positive subjects and amyloid negative healthy controls respectively. Lower Aβ1–42 (374 ± 13 ng/L versus 434 ± 23 ng/L; P < 0.05) and Aβ42/40 ratio (0.48 ± 0.2 versus 0.58 ± 0.3; P < 0.01) were observed in amyloid positive ε4 carriers versus non-carriers respectively. In healthy controls and MCI we observed a different relationship between biomarkers of amyloid-β42 and Tau or P-Tau in amyloid positive versus amyloid negative subjects. It is suggested, that a threshold of amyloid pathology may be needed to initiate T-Tau and P-Tau increase in CSF. Our results suggest a bimodal model for Aβ biomarkers, with different behavior above or below this threshold.

[P2–211]: AMYLOID‐β42 (aβ42) DIFFERENTIALLY CORRELATES WITH CSF TOTAL AND HYPERPHOSPHORYLATED TAU IN AN AMYLOID‐POSITIVE VERSUS AMYLOID‐NEGATIVE EARLY PRODROMAL AND ASYMPTOMATIC AT‐RISK FOR AD POPULATION