Abstract
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Objectives In the study of the natural course of Alzheimer disease (AD) pathology in cognitively normal adults, we have recently characterized the rate of transition to beta-amyloid (Aβ) positivity using PIB PET. Here we have evaluated beta-amyloid (Aβ) deposition on the first (“baseline”) PIB PET scan (PIB-1) and its relationship to the levels of CSF Aβ42, tau, and p-tau.
Methods Standardized uptake value ratio (SUVR) corrected for partial volume effect using a regional spread function approach was calculated for cortical gray matter regions defined with FreeSurfer software. PIB-positivity was defined using the mean cortical SUVR from precuneus, prefrontal and temporal cortical FreeSurfer ROIs; the threshold for PIB-positivity was an SUVR of 1.4. Levels of CSF Aβ42, tau and p-tau181 were obtained by ELISA.
Results Sixty seven individuals were PIB-negative on all PET scans (PIBnn); 11 individuals who were PIB-negative on the PIB-1 scan demonstrated PIB-positivity on the follow-up PET scan (PIBnp); 18 individuals were PIB-positive on all PET scans (PIBpp). At the time of PIB-1 scan, PIBnp demonstrated higher levels of mean cortical PIB deposition compared to PIBnn and lower values compared to PIBpp; CSF Aβ42 in PIBnp were lower compared to PIBnn and higher compared to PIBpp. A high correlation between PIB and CSF Aβ42 was demonstrated for mean cortical SUVR in PIBnp (R=-0.906, p < 0.001; Pearson correlation); the correlation was lower but significant in PIBpp (R=-0.551, p=0.018) and not significant in PIBnn. All participants remained cognitively normal throughout the follow-up period.
Conclusions Our findings suggest that reductions in CSF Aβ42 are coupled with amyloid deposition throughout the process of Aβ accumulation and appear to begin years prior to reaching the global brain threshold for increased Aβ deposition detected by amyloid imaging.
Research Support P50AG05681, P01AG03991, and P01AG026276