Background: The development of Alzheimer disease (AD) pathology in cognitively normal (CN) adults can be characterized by the rate of transition to beta-amyloid (Aβ) positivity with PIB PET. Here we evaluate the appearance of regional beta-amyloid (Aβ) deposition using serial PIB PET scans in relation to the levels of CSF A β 42 for detection of AD pathology in CN older adults.
      Methods: Standardized uptake value ratio (SUVR), corrected for partial volume effect using a regional spread function approach, was calculated for cortical gray matter and subcortical regions of interest (ROI) 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 A β 42 were obtained by ELISA (interval between CSF and PIB-1 measurements 0.1 ± 0.7 years).
      Results: Sixty-seven individuals were PIB-negative on both PET scans (PIBnn); 11 individuals who were PIB-negative on the PIB-1 scan demonstrated PIB-positivity on the follow-up (interval between scans 4.6 ± 2.1 years) PET scan (PIBnp); 18 individuals were PIB-positive on both PET scans (PIBpp). All participants remained CN throughout the follow-up period. At the time of PIB-1 scan, PIBnp demonstrated higher levels of regional and mean cortical PIB deposition compared to PIBnn and lower values compared to PIBpp; CSF A β 42 in PIBnp were lower compared to PIBnn and higher compared to PIBpp. A high correlation between PIB and CSF A β 42 was demonstrated for mean cortical region and ROIs in prefrontal and parietal cortex in PIBnp; the correlation for these ROIs was lower but significant in PIBpp, and not significant in PIBnn.
      Conclusions: Our findings suggest that reductions in CSF Aβ42 are coupled with regional amyloid deposition throughout the process of Aβ accumulation and are evident years prior to reaching the global brain threshold for preclinical AD detected by amyloid imaging.