Assessing global and regional Aβ-amyloid deposition in the brain with multiple Aβ-tracers using the Centiloid scale

Abstract

Background: The aim of the study was to evaluate if Centiloids (CL) generated with different Aβ tracers yielded similar rates of Aβ accumulation, validating its use in multicenter, multitracer anti-Aβ therapeutic trials.

Methods: We used longitudinal Aβ imaging data from the AIBL and ADNI studies to calculate the rates of global and regional Aβ-amyloid deposition. We analyzed 485 participants from AIBL and ADNI (321 HC; 135 MCI; 29 AD) with 3 or more Aβ imaging assessments. While AIBL participants underwent Aβ imaging with PiB and NAV4694 (n=220, median follow-up of 4.8 -range 2.5-10.6- years), or flutemetamol (FLUTE, n=94, median follow-up of 3.2 -range 3.0-3.8- years), ADNI participants underwent Aβ imaging with florbetapir (FBP, n=171, median follow-up of 4.1 -range 2.9-5.7 - years). CL were generated using the CL cortical and whole cerebellum masks. FBP SUVR were first generated using a white matter mask and then converted to whole cerebellum before the CL transformation. Aβ accumulation was derived from the slope of the linear regression plots, and rates of accumulation were calculated from the time it took to go from a threshold 20 CL (Aβ-) to 100 CL (mean levels of Aβ+AD).

Results: Of 485 initial participants, 417 (86%) (270 HC; 118 MCI; 29 AD) showed positive rates of Aβ accumulation over 3 or more assessments. Irrespective of the Aβ tracer used, Aβ deposition spans more than two decades, averaging 22.7±3.9 (mean±SD) years to go from a threshold of 20 CL to 100 CL. Rates of Aβ accumulation were 3.8 CL/yr (5%/yr) for PiB/NAV, 3.6 CL/yr (5%/yr) for FLUTE and 3.0 CL/yr (4%/yr) for FBP, respectively, averaging 3.5±0.4 CL/yr (4.3%/yr) when all tracers are considered together. The regional assessment showed fastest Aβ accumulation in the posterior cingulate/precuneus and frontal areas, and slowest in the hippocampus.

Conclusions: Aβ-amyloid deposition is a slow and protracted process, extending for more than two decades. Centiloids can be used to combine longitudinal Aβ imaging data obtained with different Aβ tracers.