Apolipoprotein E Genotype Affects Size of ApoE Complexes in Cerebrospinal Fluid
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Apolipoprotein E (apoE) is associated with lipoproteins in the cerebrospinal fluid (CSF). APOE4 increases and APOE2 decreases the risk for Alzheimer disease (AD) compared to the risk associated with APOE3 Because apoE4 is less efficient at cholesterol efflux than apoE2 or apoE3 in vitro, we hypothesized that APOE genotype may affect apoE particle size in vivo and that these size differences may be related to AD risk. We used nondenaturing gel electrophoresis to test for differences in the size of apoE complexes in human CSF samples of various APOE genotypes and created profiles of each sample to compare the patterns of apoE distribution. For middle-aged adults with no dementia, APOE 2.3 individuals had significantly larger apoE complexes than APOE 3.3 subjects, who had significantly larger apoE complexes than APOE 3.4 and APOE 4.4 individuals. Similarly, in an independent cohort of older adults, CSF apoE complexes of APOE4-positive individuals were smaller than those of the APOE4-negative individuals. Compared to individuals with no dementia, those with the mildest stages of dementia had similar sized CSF apoE complexes. These results identify a novel phenotypic difference in the size of CSF apoE complexes in middle age that correlate with the risk of AD later in life.
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ApoE lipidation is a crucial factor in Alzheimer's disease pathogenesis.
“These small, poorly lipidated apoE particles are similar in size to apoE ε4 particles, further highlighting apoE lipidation as a crucial factor in AD pathogenesis. 8 , 9”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [8]
Small, poorly lipidated apoE particles are similar in size to apoE ε4 particles.
“These small, poorly lipidated apoE particles are similar in size to apoE ε4 particles, further highlighting apoE lipidation as a crucial factor in AD pathogenesis. 8 , 9”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [8]
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Lipoprotein Particles in Cerebrospinal Fluid
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- Authors
- Heinsinger, N. M., Gachechiladze, M. A., & Rebeck, G. W.
- Affiliations
- Georgetown University (US)
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-11
- Volume
- 75
- Issue
- 10
- Pages
- 918-924
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC6996536
- OpenAlex
- W2517337661
- Cited by
- 74
- References
- 48
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 12 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 12 · 2019: 8 · 2018: 1 · 2017: 3 · 2016: 1
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Washington University in St. Louis
- Georgetown University
- National Institutes of Health
- National Institute on Aging (P01AG030128, P50AG005681)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, APOE genotype, cerebrospinal fluid, particle size, Alzheimer's disease risk, APOE ε4, APOE2, APOE3, cholesterol efflux, dementia, lipoproteins
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