Report Anne M. Fagan et al. Figure 1. Cortical amyloid as detected by PET PIB and fluid biomarkers in CDR 0 participants (n ¼ 189) as a function of age. Levels of A. cortical amyloid are positively correlated with age in this CDR 0 cohort, B. The level of CSF Ab38 is not correlated with age, C. nor is CSF Ab40. D. CSF Ab42 is negatively correlated with age. E. Positive correlations with age are observed for CSF tau, F. CSF ptau181 and G. plasma Ab1–40. H. Plasma Ab1–42 is not correlated with age in this cohort. not related to the presence or amount of cortical amyloid in these individuals (Fig 2D). Similarly, levels of CSF Ab38 were not correlated with cortical amyloid load (Fig 2E), but the ratio of CSF Ab38/Ab42 was positively correlated with amyloid load (Fig 2F), likely due to the drop in CSF Ab42 with amyloid deposition. Twenty-eight CDR 0 individuals showed a mismatch, appearing in the ‘lower quadrant’ of Fig 2B (whose boundaries are indicated by the square outlined in a dashed line in Fig 2B) in that they had little or no cortical PIB binding (MCPB < 0.18) but had low CSF Ab42 (<500 pg/ml). The mean interval between LP and PIB scans for individuals in this quadrant did not differ statistically from the mean intervals of those participants in the other quadrants (i.e. low PIB/high CSF Ab42 and high PIB/low CSF Ab42) ( p ¼ 0.4693). In addition, this low PIB/low CSF Ab42 group (‘lower quadrant’, n ¼ 28) did not differ from the low PIB/high CSF Ab42 group (‘upper quadrant’, n ¼ 132) in the frequency of the e4 allele of APOE (39% vs. 27%, respectively, p ¼ 0.2049), nor did it differ from the high PIB/low CSF Ab42 (‘PIB-positive quadrant’) group (39% vs. 62%, respectively), but it did approach statistical signiﬁcance ( p ¼ 0.0854). The e4þ frequency in the high PIB/low CSF Ab42 (‘PIB-positive www.embomolmed.org EMBO Mol Med 1, 371–380 2009 EMBO Molecular Medicine 373