Assessing the natural history of Aß-amyloid deposition with five different amyloid tracers using the Centiloid transformation

Objectives: We calculated the rates of global and regional Aβ-amyloid deposition from up to 10 years of longitudinal Aβ-imaging data.

Methods: Two-hundred-and-three participants (149 controls; 34 MCI; 20 AD) were evaluated at enrolment and every 18 months for a mean follow-up of 4.9 (range 2.5-10.6) years. A 1.4 PiB SUVR (25 Centiloids -CL-) was used to discriminate between high (Aβ+) from low (Aβ-) Aβ burdens. Rates of Aβ deposition were derived from the slope of the linear regression plots. Irrespective of their Aβ status, participants with a positive rate of Aβ deposition, deemed to be on the “AD-pathway,” were used for the analyses. The same approach was used to establish the rates of Aβ accumulation as assessed by ¹⁸F-flutemetamol, ¹⁸F-florbetapir, and ¹⁸F-florbetaben

Results: At baseline, significantly higher global Aβ burdens were observed in AD (2.3±0.4 SUVR/91±26 CL) and MCI (2.0±0.7 SUVR/77±27 CL) when compared to controls (1.4±0.4 SUVR/25±7 CL). At follow-up 164 (82%) participants showed positive rates of Aβ accumulation. Confirming our previous findings, Aβ deposition spans more than two decades, averaging 30 (CI 25-39) years to go from the levels observed in Aβ- controls (1.2±0.1 SUVR/10±1 CL) to those observed in mild AD, with rates of 0.048 -CI 0.041-0.056- SUVR/yr (3.8 -CI 3.2-4.4- CL/yr), between the 1.4 SUVR threshold of abnormality to the 2.3 SUVR observed in AD. As AD progresses, the rate of Aβ deposition slows, approaching a plateau. Similar results were obtained with the other tracers, suggesting that longitudinal results can be pooled together when expressed in CL.

Conclusion: Our new assessment with a longer follow-up confirmed our previous findings that Aβ-amyloid deposition is a slow and protracted process, extending for more than two decades. Research Support: .