Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer disease
Abstract
This study examines the relationship between the levels of apolipoprotein E (apoE) and apolipoprotein J (apoJ, also designated as clusterin) as a function of apoE genotype in the hippocampus and cortex of Alzheimer disease (AD) subjects. These two lipophilic proteins which are involved in the maintenance of lipid homeostasis are both synthesized in the brain by astrocytes. Results indicate a reduction of apoE levels in the hippocampus and frontal cortex that is proportional to the apoE4 allele dose. Conversely, apoJ (clusterin) levels were found to increase proportionately to the number of apoE4 allele dose. These results suggest a compensatory induction of apoJ (clusterin) in the brain of apoE4 AD subjects showing low brain levels of apoE.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The effect of the ε4 allele on locally synthesized CNS apoE protein levels is less clear, with conflicting reports showing reduced levels, no change, or increases in apoE from AD patient CNS and animal models.
“The effect of the 4 allele on the locally synthesized CNS apoE protein levels is less clear with multiple conflicting reports showing either reduced levels (Bertrand et al., 1995;Beffert et al., 1999;Glo ¨ckner et al., 2002;Poirier, 2005;Ramaswamy et al., 2005), no change (Sullivan et al., 2004;Fryer et al., 2005) or increases (Fukumoto et al., 2003) in apoE from both AD patient CNS and animal mo”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Bertrand et al., 1995
PICALM is involved in clathrin-mediated endocytosis, an essential step in intracellular trafficking of proteins and lipids.
“It has been shown that like BIN1, PICALM is involved in clathrinmediated endocytosis (CME), an essential step in the intracellular trafficking of proteins and lipids such as nutrients, growth factors and neurotransmitters 36-38.”
From Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (2009) · cites this paper as [36]
A number of studies investigating apoE expression and protein levels in the brain parenchyma as a function of APOE genotype have yielded controversial results.
“A number of studies investigating apoE expression and protein levels in the brain parenchyma as a function of APOE genotype have yielded controversial results (Beffert et al., 1999b; Bertrand et al., 1995; Bray et al., 2004; Growdon et al., 1999; Harr et al., 1996; Lambert et al., 1997; Pirttila et al., 1996).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Bertrand et al., 1995
Cites
Abnormal in vivo metabolism of apolipoprotein E4 in humans.
Gregg, R. E., Zech, L. A., Schaefer, E. J., Stark, D., Wilson, D., & Brewer, H. B. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112645 · Cited by 345 · see citing works
May, P. C., Lampert-Etchells, M., Johnson, S. A., Poirier, J., Masters, J. N., & Finch, C. E. (1990) · Neuron · doi:10.1016/0896-6273(90)90342-d · Cited by 339 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
Epidemiology of Alzheimer disease
Reitz, C., Brayne, C., & Mayeux, R. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.2 · Cited by 1,675 · see citing works
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward
Belloy, M. E., Napolioni, V., & Greicius, M. D. (2019) · Neuron · doi:10.1016/j.neuron.2019.01.056 · Cited by 570 · see citing works
Genetic Association of Apolipoprotein E with Age-Related Macular Degeneration
Klaver, C. C. W., Kliffen, M., van Duijn, C. M., Hofman, A., Cruts, M., Grobbee, D. E., van Broeckhoven, C., & de Jong, P. T. V. M. (1998) · The American Journal of Human Genetics · doi:10.1086/301901 · Cited by 498 · see citing works
Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., Xu, L., Aschmies, S., Kirksey, Y., Hu, Y., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1972-08.2008 · Cited by 342 · see citing works
Fernandez, C. G., Hamby, M. E., McReynolds, M. L., & Ray, W. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00014 · Cited by 277 · see citing works
APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease
Youmans, K. L., Tai, L. M., Nwabuisi-Heath, E., Jungbauer, L., Kanekiyo, T., Gan, M., Kim, J., Eimer, W. A., Estus, S., Rebeck, G. W., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.407957 · Cited by 259 · see citing works
Bien-Ly, N., Gillespie, A. K., Walker, D., Yoon, S. Y., & Huang, Y. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0033-12.2012 · Cited by 170 · see citing works
APOE Stabilization by Exercise Prevents Aging Neurovascular Dysfunction and Complement Induction
Soto, I., Graham, L. C., Richter, H. J., Simeone, S. N., Radell, J. E., Grabowska, W., Funkhouser, W. K., Howell, M. C., & Howell, G. R. (2015) · PLOS Biology · doi:10.1371/journal.pbio.1002279 · Cited by 140 · see citing works
White, F., Nicoll, J. A. R., Roses, A. D., & Horsburgh, K. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0401 · Cited by 128 · see citing works
Nilselid, A.-M., Davidsson, P., Nägga, K., Andreasen, N., Fredman, P., & Blennow, K. (2006) · Neurochemistry International · doi:10.1016/j.neuint.2005.12.005 · Cited by 104 · see citing works
Cholinergic systems and long-term potentiation in memory-impaired apolipoprotein E-deficient mice
Krzywkowski, P., Ghribi, O., Gagné, J., Chabot, C., Kar, S., Rochford, J., Massicotte, G., & Poirier, J. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00061-5 · Cited by 74 · see citing works
Self-citationApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease
Li, Y., Macyczko, J. R., Liu, C.-C., & Bu, G. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.03.011 · Cited by 61 · see citing works
In Vivo Human Apolipoprotein E Isoform Fractional Turnover Rates in the CNS
Wildsmith, K. R., Basak, J. M., Patterson, B. W., Pyatkivskyy, Y., Kim, J., Yarasheski, K. E., Wang, J. X., Mawuenyega, K. G., Jiang, H., Parsadanian, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038013 · Cited by 54 · see citing works
“isoform status on ApoE protein levels in the CSF [19,23,33–35] and brain [20,36–38].”
BackgroundApolipoprotein J (clusterin) activates rodent microglia <i>in vivo</i> and <i>in vitro</i>
Xie, Z., Harris‐White, M. E., Wals, P. A., Frautschy, S. A., Finch, C. E., & Morgan, T. E. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03065.x · Cited by 53 · see citing works
Introducing Human <i>APOE</i> into A<i>β</i> Transgenic Mouse Models
Tai, L. M., Youmans, K. L., Jungbauer, L., Yu, C., & LaDu, M. J. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/810981 · Cited by 52 · see citing works
ApoE expression across the CNS: Who, What, Where, When, and How (much)?
Nolt, G. L., Lucido, C. C., Smith, L. M., & Johnson, L. A. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00028-x · Cited by 2 · see citing works
- Authors
- Bertrand, P., Poirier, J., Oda, T., Finch, C. E., & Pasinetti, G. M.
- Affiliations
- McGill University (CA)
- Douglas Mental Health University Institute (CA)
- University of Southern California (US)
- Corresponding author
- Poirier, Judes
- Venue
- Molecular Brain Research
- Publisher
- Elsevier BV
- Published
- 1995-10
- Volume
- 33
- Issue
- 1
- Pages
- 174-178
- ISSN
- 0169-328X (ISSN-L)
- OpenAlex
- W2070716601
- Cited by
- 210
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 2 · 2022: 12 · 2021: 9 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 9 · 2015: 9 · 2014: 7 · 2013: 9 · 2012: 9
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag010003-03)
- Medical Research Council
- National Institute on Aging (AG10003-01)
- 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 › Oncology › Clusterin in disease pathology
- Keywords
- apolipoprotein E, clusterin, Alzheimer's disease, hippocampus, frontal cortex, astrocytes, lipid homeostasis, gene expression
- MeSH terms
- Alzheimer Disease, Apolipoproteins E, Frontal Lobe, Genotype, Glycoproteins, Hippocampus, Humans, Nerve Tissue Proteins, Solubility, Case-Control Studies, Molecular Chaperones, Clusterin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
