O5–02–03: Regional distribution of brain fibrillar amyloid deposition 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 [11 C]PIB or [18 F]florbetapir) and CSF Aβ 1–42, t-tau, p-tau, global [18 F]FDG (SUVR). A total of 253 subjects (CN 54, EMCI 128, LMCI 40, AD 31) from ADNI dataset were analyzed. CSF Aβ 1–42, t-tau, p-tau and PET scan were obtained in the same individual not more than 6 months apart. Voxel-based SUVR maps for [11 C]PIB and [18 F]florbetapir 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 Aβ 1–42 and regional [18 F]florbetapir or [11 C]PIB binding were better described by an exponential decay model. The associations between Aβ 1–42 and [18 F]florbetapir or [11 C]PIB were similar in frontal, posterior parietal, temporal, precuneus and posterior cingulated areas (t>4.5; Figure 1). No associations between Aβ 1–42 and amyloid imaging agents were observed in the white matter and brain stem regions. Individuals with CSF Aβ 1–42 value over 200 pg/mL did not show [11 C]PIB 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 [11 C]PIB uptake in a small cluster in the frontal area. In contrast, CSF t-tau or p-tau showed correlation with [18 F]florbetapir in frontal, temporal and parietal brain regions. No correlation was shown between global [18 F]FDG 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 A b 1–42 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, [18 F]FDG uptake seems to provide independent information from regional deposition of fibrillary amyloid. (A) showed the association between [C]PIB and CSF biomarkers, [F]FDG(SUVr). (B) showed the association between [F]florbetapir and CSF biomarkers, [F] FDG(SUVr).

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