ApoE4: is it the absence of good or the presence of bad?
Abstract
It is well established that ApoE genotype is highly associated with the risk of developing Alzheimer’s disease (see Ashford & Mortimer discussion in Debate 3, this volume). The establishment of this association has led to an intense search for the role that ApoE plays in brain function, particularly in functions such as neuroplasticity that are most involved with the Alzheimer neuropathological process. In the course of this search, results have tended to show either that the ApoE e-3 protein has some beneficial effect, or the e-4 protein has some harmful effect. The issue in this debate hinges around this point, which perspective is most sound? Whether the e-3 protein helps to protect the brain from Alzheimer pathology (e-3 good) or the e-4 protein directly instigates the pathological process (e-4 evil)? The debate on the goodness of ApoE e3 or the badness of ApoE e4, in Cincinnati in July, 2001, and in the written summaries both reflect the dichotomous positions of the roles attributed to the different ApoE alleles. The disparity of the two sides and the importance of this issue were most clearly framed at the beginning of the summary statement by Rebeck et al., in relating the issue to treatment decisions:
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There has been intense debate as to whether potential Alzheimer's disease therapeutics should increase or decrease apoE levels.
“There has been intense debate as to whether potential AD therapeutics should increase or decrease apoE levels (Ashford, 2002; Rebeck et al., 2002; Teter et al., 2002; Osherovich, 2009).”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Ashford, 2002
There is still debate regarding whether increasing or decreasing apoE is the best strategy in regard to AD therapeutics.
“The role of apoE in AD pathogenesis has been studied extensively, but there is still debate regarding whether increasing or decreasing apoE is the best strategy in regard to AD therapeutics (Ashford, 2002;Teter et al., 2002).”
From Anti-ApoE Antibody Given after Plaque Onset Decreases Aβ Accumulation and Improves Brain Function in a Mouse Model of Aβ Amyloidosis (2014) · cites this paper as Ashford, 2002
Cites
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Kim, J., Jiang, H., Park, S., Eltorai, A. E. M., Stewart, F. R., Yoon, H., Basak, J. M., Finn, M. B., & Holtzman, D. M. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3773-11.2011 · Cited by 199 · see citing works
“There has been intense debate as to whether potential AD therapeutics should increase or decrease apoE levels (Ashford, 2002; Rebeck et al., 2002; Teter et al., 2002; Osherovich, 2009).”
BackgroundLiao, F., Hori, Y., Hudry, E., Bauer, A. Q., Jiang, H., Mahan, T. E., Lefton, K. B., Zhang, T. J., Dearborn, J. T., Kim, J., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0646-14.2014 · Cited by 128 · see citing works
“The role of apoE in AD pathogenesis has been studied extensively, but there is still debate regarding whether increasing or decreasing apoE is the best strategy in regard to AD therapeutics (Ashford, 2002; Teter et al., 2002).”
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Self-citationThe Dichotomy of Alzheimer’s Disease Pathology: Amyloid-β and Tau
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Now is the Time to Improve Cognitive Screening and Assessment for Clinical and Research Advancement
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Self-citation
- Authors
- Ashford, J. W.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Ashford, J. Wesson
- ORCID
- Ashford, J. Wesson
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2002-07-23
- Volume
- 4
- Issue
- 3
- Pages
- 141-143
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1800360917
- Cited by
- 21
- References
- 3
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, APOE ε4
- MeSH terms
- Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Humans, Risk, Amyloid beta-Peptides, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2
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