Journal ArticleDOI
Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging.
Veer Bala Gupta,Veer Bala Gupta,Simon M. Laws,Simon M. Laws,Victor L. Villemagne,David Ames,Ashley I. Bush,Kathryn A. Ellis,James Lui,James Lui,Colin L. Masters,Christopher C. Rowe,Cassandra Szoeke,Kevin Taddei,Kevin Taddei,Ralph N. Martins +15 more
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TLDR
Analysis of cross-sectional data from the AIBL study indicates that plasma apoE levels are altered in AD and correlate with AD pathology level.Abstract:
Objective: There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which included both healthy controls and participants with early-stage AD. Methods: Total apoE and apoE4 were measured in 1,079 individuals drawn from the highly characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Total and isoform-specific plasma apoE levels were then compared with cerebral Aβ load, as assessed by PET using Pittsburgh compound B (PiB). Results: Total apoE and apoE4 levels were found to be significantly lower in patients with AD in the entire cohort, and decrease with Aβ load in the PiB-PET subset. ApoE levels were significantly lower among ϵ4 homozygous individuals. In APOE ϵ3/ϵ4 heterozygote carriers, apoE4 levels decrease, indicating that apoE3 levels increase with disease. Conclusion: Analysis of cross-sectional data from the AIBL study indicates that plasma apoE levels are altered in AD and correlate with AD pathology level. The significance of these findings will be determined in the AIBL longitudinal study of aging.read more
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Journal ArticleDOI
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
TL;DR: The A β-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk are discussed, and how to design effective strategies for AD therapy by targeting ApO-E is considered.
Journal ArticleDOI
Blood-Based Protein Biomarkers for Diagnosis of Alzheimer Disease
James D. Doecke,James D. Doecke,Simon M. Laws,Simon M. Laws,Noel G. Faux,Noel G. Faux,William Wilson,Samantha C. Burnham,Chiou Peng Lam,Alinda Mondal,Alinda Mondal,Justin Bedo,Ashley I. Bush,Ashley I. Bush,Belinda M. Brown,Belinda M. Brown,Karl De Ruyck,Karl De Ruyck,Kathryn A. Ellis,Christopher Fowler,Veer Bala Gupta,Veer Bala Gupta,Richard Head,S. Lance Macaulay,Kelly K. Pertile,Christopher C. Rowe,Alan Rembach,Mark Rodrigues,Mark Rodrigues,Rebecca L. Rumble,Cassandra Szoeke,Kevin Taddei,Kevin Taddei,Tania Taddei,Tania Taddei,Brett Trounson,David Ames,Colin L. Masters,Colin L. Masters,Ralph N. Martins,Ralph N. Martins +40 more
TL;DR: This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity.
Journal ArticleDOI
Apolipoprotein E in Alzheimer's Disease: An Update
Jin-Tai Yu,Lan Tan,John Hardy +2 more
TL;DR: Emerging data suggest that APOE contributes to AD pathogenesis through both amyloid-β (Aβ)-dependent and Aβ-independent pathways and the utility of APOE genotyping in AD diagnosis, risk assessment, prevention, and treatment response is suggested.
Journal ArticleDOI
Amyloid-β-independent regulators of tau pathology in Alzheimer disease.
TL;DR: Novel insights from preclinical research are outlined that implicate apolipoprotein E, the endocytic system, cholesterol metabolism and microglial activation as Aβ-independent regulators of tau pathology in Alzheimer disease.
Journal ArticleDOI
The future of blood-based biomarkers for Alzheimer's disease
Kim Henriksen,Sid E. O'Bryant,Harald Hampel,John Q. Trojanowski,Thomas J. Montine,Andreas Jeromin,Kaj Blennow,Anders Lönneborg,Tony Wyss-Coray,Holly Soares,Chantal Bazenet,Magnus Sjögren,William T. Hu,Simon Lovestone,Morten A. Karsdal,Michael W. Weiner +15 more
TL;DR: The points addressed include: the major challenges in the development of blood‐based biomarkers of AD, including patient heterogeneity, inclusion of the “right” control population, and the blood–brain barrier; the need for standardization of preanalytical variables and analytical methodologies used by the field.
References
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Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Warren J. Strittmatter,Ann M. Saunders,Donald E. Schmechel,Margaret A. Pericak-Vance,Jan J. Enghild,Guy S. Salvesen,Allen D. Roses +6 more
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TL;DR: Data support the involvement of ApoE ϵ4 in the pathogenesis of late-onset familial and sporadic AD and suggest it may operate as a susceptibility gene (risk factor) for the clinical expression of AD.
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