apo e4
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Introduction
Structure
Pathology
- associated with 50% of familial late-onset Alzheimer's disease (AD)
- each apo-E4 allele confers a 3-4-fold increased risk of AD[7][13][14][15]
- 2-fold risk of AD among women[6]
- only slight increase in risk of AD among men[6]
- most patients with AD do not carry the apo E4 allele[7]
- 48% overall, 61% in Northern Europe[10]
- each apo-E4 allele confers a 3-4-fold increased risk of AD[7][13][14][15]
- cortical thickness of the left entorhinal cortex is lowest in children with the apoE4 allele < apoE3 < apoE2[11]
- apo E4 may also be a risk factor for amyloid angiopathy, independent of AD[3]
- the apo E4 allele is associated with a significantly higher amyloid plaque burden than observed with the apo E3 & apo E2 alleles
- the higher amyloid plaque burden & risk of AD may related to differential binding of apo E4 to the A4 amyloid peptide or differential processing of A4-bound apo E4
- thus apo E4 appears to enhance A4 deposition in the brain, especially A4/40 by diminishing A4 clearance[4].
- the burden of neurofibrillary tangles is allegedly not as sensitive to the apo E4 allele as the burden of amyloid plaques
- apo E4 may also carry a 4-fold higher risk of cardiovascular disease[5]
- cognitive impairment in patients with early Parkinson's disease & the apoE4 allele may be mitigated by exercise[12]
Laboratory
More general terms
Additional terms
- Alzheimer's disease (ADD)
- apolipoprotein E genotype
- apolipoprotein-E gene
- cerebral amyloid angiopathy (CAA)
References
- ↑ Mendelian Inheritance in Man (1990) MIM#107741
- ↑ Strittmatter WJ et al Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8446617
- ↑ 3.0 3.1 Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 2352
- ↑ 4.0 4.1 Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11274343
- ↑ 5.0 5.1 Rutlege JC, UC Davis Dept of Medicine Grand Rounds, Aug 2, 2007
- ↑ 6.0 6.1 6.2 Altmann A et al Sex modifies the APOE-related risk of developing Alzheimer disease. Annals of Neurology. April 14, 2014 http://onlinelibrary.wiley.com/doi/10.1002/ana.24135/abstract
- ↑ 7.0 7.1 7.2 Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ Bu G. Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy. Nat Rev Neurosci. 2009 May;10(5):333-44. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19339974 Free PMC Article
- ↑ Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013 Feb;9(2):106-18. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23296339 Free PMC Article
- ↑ 10.0 10.1 Ward A, Crean S, Mercaldi CJ et al Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4/4) among patients diagnosed with Alzheimer's disease: a systematic review and meta-analysis. Neuroepidemiology. 2012;38(1):1-17. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22179327 Free Article
- ↑ 11.0 11.1 Shaw P, Lerch JP, Pruessner JC et al Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study. Lancet Neurol. 2007 Jun;6(6):494-500. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17509484
- ↑ 12.0 12.1 Kim R, Park S, Yoo D et al. on Association of physical activity and APOE genotype with longitudinal cognitive change in early PD. Neurology 2021 Mar 31; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/33790041 https://n.neurology.org/content/early/2021/03/31/WNL.0000000000011852
- ↑ 13.0 13.1 Lane-Donovan C, Herz J. ApoE, ApoE Receptors, and the synapse in Alzheimer's disease. Trends Endocrinol Metab. 2017;28(4):273-284 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28057414 PMCID: PMC5366078Free PMC article https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(16)30170-9
- ↑ 14.0 14.1 Uddin MS, Kabir MT, Al Mamun A et al. APOE and Alzheimer's disease: evidence mounts that targeting APOE4 may combat Alzheimer's pathogenesis. Mol Neurobiol. 2019;56(4):2450-2465 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30032423 https://link.springer.com/article/10.1007/s12035-018-1237-z
- ↑ 15.0 15.1 Zhao N, Liu CC, Qiao W, et al. Apolipoprotein E, receptors, and modulation of Alzheimer's disease. Biol Psychiatry. 2018;83(4):347-357 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28434655 PMCID: PMC5599322Free PMC article https://www.biologicalpsychiatryjournal.com/article/S0006-3223(17)31358-6/fulltext