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.