TY - JOUR
T1 - Mapping the effects of ApoE4, age and cognitive status on 18F-florbetapir PET measured regional cortical patterns of beta-amyloid density and growth
AU - Murphy, Kelly R.
AU - Landau, Susan M.
AU - Choudhury, Kingshuk Roy
AU - Hostage, Christopher A.
AU - Shpanskaya, Katie S.
AU - Sair, Haris I.
AU - Petrella, Jeffrey R.
AU - Wong, Terence Z.
AU - Doraiswamy, P. Murali
N1 - Funding Information:
Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904 ). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514 . KRM's research was supported in part by the Wrenn Clinical Research Scholar fund.
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - 18F-florbetapir PET
KW - Alzheimer's disease
KW - ApoE4
KW - Beta-amyloid deposition
UR - http://www.scopus.com/inward/record.url?scp=84877910278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877910278&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2013.04.048
DO - 10.1016/j.neuroimage.2013.04.048
M3 - Article
C2 - 23624169
AN - SCOPUS:84877910278
VL - 78
SP - 474
EP - 480
JO - NeuroImage
JF - NeuroImage
SN - 1053-8119
ER -