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

- Cortical regions measured showed β-amyloid increases over Alzheimer's development.
- Regional cortical β-amyloid growth occurs in an ApoE genotype specific manner.
- Regional cortical β-amyloid density on florbetapir PET is higher in women than men.
- The effect of Age on cortical β-amyloid is much weaker than the effect of ApoE4.

BackgroundAlthough 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.MethodsWe 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).FindingsIn 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).InterpretationNeuritic 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.