Mapping the effects of ApoE4, age and cognitive status on 18F-florbetapir PET measured regional cortical patterns of beta-amyloid density and growth

Background: Although it is well known that many clinical and genetic factors have been associated with beta-amyloid deposition, few studies have examined the interactions of such factors across different stages of Alzheimer's pathogenesis. Methods: We used 18F-florbetapir F18 PET imaging to quantify neuritic beta-amyloid plaque density across four cortical regions in 602 elderly (55-94. years) subjects from the national ADNI biomarker study. The group comprised of 194 normal elderly, 212 early mild cognitive impairment [EMCI], 132 late mild cognitive impairment [LMCI], and 64 mild Alzheimer's (AD). Findings: In a model incorporating multiple predictive factors, the effect of apolipoprotein E ε4 and diagnosis was significant on all four cortical regions. The highest signals were seen in cingulate followed by frontal and parietal with lowest signals in temporal lobe (p. <. 0.0001). The effect of apolipoprotein E ε4 (Cohen's D 0.96) on beta-amyloid plaque density was approximately twice as large as the effect of a diagnosis of AD (Cohen's D 0.51) and thrice as large as the effect of a diagnosis of LMCI (Cohen's D 0.34) (p. <. 0.0001). Surprisingly, ApoE ε4. + normal controls had greater mean plaque density across all cortical regions than ε4. - EMCI and ε4. - LMCI (p. <. 0.0001, p. =. 0.0009) and showed higher, though non-significant, mean value than ε4. - AD patients (p. <. 0.27). ApoE ε4. + EMCI and LMCI subjects had significantly greater mean plaque density across all cortical regions than ε4. - AD patients (p. <. 0.027, p. <. 0.0001). Interpretation: Neuritic amyloid plaque load across progressive clinical stages of AD varies strongly by ApoE4 genotype. These findings support the need for better pathology-based and supported diagnosis in routine practice. Our data also provides additional evidence for a temporal offset between amyloid deposition and clinically relevant symptoms.