IC‐P‐011: Regional distribution of fibrillar amyloid deposition in the brain as a function of CSF beta‐amyloid 1–42 and biomarkers of neurodegeneration

Fibrillar amyloid deposition is one of the main features of Alzheimer's disease (AD) and occurs in various cortical regions. Although age and APOE4 status contribute to global amyloidosis, factors involved on regional deposition of fibrillary amyloid are currently unknown. Here, we described associations between regional fibrillar amyloid deposition (measured with 11CPIB or 18Fflorbetapir) and CSF Aβ1–42, t-tau, p-tau, global 18FFDG (SUVR). A total of 253 subjects (CN 54, EMCI 128, LMCI 40, AD 31) from ADNI dataset were analyzed. CSF Aβ1–42, t-tau, p-tau and PET scan were obtained in the same individual not more than 6 months apart. Voxel-based SUVR maps for 11CPIB and 18Fflorbetapir were calculated using the cerebellar cortex as a reference region. Global SUV was estimated as the median SUVR value obtained using masks encompassing fronto-temporo-parietal regions. A cross-sectional linear and non-linear analysis was conducted between CSF and imaging biomarkers. Demographic data is presented in Table 1. The associations between CSF Aβ1–42 and regional 18Fflorbetapir or 11CPIB binding were better described by an exponential decay model. The associations between Aβ1–42 and 18Fflorbetapir or 11CPIB were similar in frontal, posterior parietal, temporal, precuneus and posterior cingulated areas (t>4.5; Figure 1). Individuals with CSF Aβ1–42 value over 200 pg/mL did not show 11CPIB uptake in cortical areas. In contrast both amyloid-imaging agents showed linear association with t-tau and p-tau. CSF t-tau and p-tau showed significant correlation with 11CPIB uptake in a small cluster in the frontal area. In contrast, CSF t-tau or p-tau showed correlation with 18Fflorbetapir in frontal, temporal and parietal brain regions. No correlation was shown between global 18FFDG SUVR and the binding of amyloid imaging agents (Figure1). The pattern of regional deposition of fibrillary amyloid in the brain is non-linearly associated with CSF Aβ1–42 concentrations. However the link between p-tau, t-tau and fibrillary amyloid deposition seems to be dependent on the amyloid-imaging agent. While imaging and CSF measures of amyloid pathology are equivalent, 18FFDG uptake seems to provide independent information from regional deposition of fibrillary amyloid. (A) showed the association between 11CPIB and CSF biomarkers, 18FFDG(SUVr). (B) showed the association between 18Fflorbetapir and CSF biomarkers, 18F FDG(SUVr).