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

NeuroImage

PubMedID: 23624169

Murphy KR, Landau SM, Choudhury KR, Hostage CA, Shpanskaya KS, Sair HI, Petrella JR, Wong TZ, Doraiswamy PM, Alzheimer's Disease Neuroimaging Initiative. Mapping the effects of ApoE4, age and cognitive status on 18F-florbetapir PET measured regional cortical patterns of beta-amyloid density and growth. Neuroimage. 2013;78474-80.
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 e4 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 e4 (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 e4+ normal controls had greater mean plaque density across all cortical regions than e4- EMCI and e4- LMCI (p<0.0001, p=0.0009) and showed higher, though non-significant, mean value than e4- AD patients (p<0.27). ApoE e4+ EMCI and LMCI subjects had significantly greater mean plaque density across all cortical regions than e4- 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.