• Kelly R Murphy, Susan M Landau, Kingshuk Roy Choudhury, Christopher A Hostage, Katie S Shpanskaya, Haris I Sair, Jeffrey R Petrella, Terence Z Wong, P Murali Doraiswamy, and Alzheimer's Disease Neuroimaging Initiative.
• Department of Psychiatry, Duke University Health System, Duke University Medical Center, Durham, NC, USA.
• Neuroimage. 2013 Sep 1;78:474-80.

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.Copyright © 2013 Elsevier Inc. All rights reserved.

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