Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions

William Rebeck, G.; Reiter, Joell S.; Strickland, Dudley K.; Hyman, Bradley T.

doi:10.1016/0896-6273(93)90070-8

Cited by 1,107Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions

William Rebeck, G., Reiter, Joell S., Strickland, Dudley K., Hyman, Bradley T.·1993·Neuron

DOI 10.1016/0896-6273(93)90070-8

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Abstract

An increased prevalence of apolipoprotein E (ApoE) epsilon 4 allele exists in late onset familial Alzheimer's disease. We found, in sporadic Alzheimer's disease, that 62% of patients possessed an ApoE-epsilon 4 allele, compared with 20% of controls. ApoE-epsilon 4/4 patients had more senile plaques (SPs) than epsilon 3/3 patients. ApoE immunoreactivity of SPs was equivalent in both groups. Two receptors bind ApoE complexes, the low density lipoprotein (LDL) receptor and the LDL receptor-related protein (LRP). In normal brain, anti-LRP antibodies strongly stained neurons and lightly stained astrocytes; anti-LDL receptor antibodies stained only the neuropil and astrocytes. In Alzheimer's disease, SPs and reactive astrocytes were also strongly LRP immunoreactive. Colocalization of ApoE and LRP to SPs implies that these molecules may be involved in metabolism of components of SPs.

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APOE4 is the strongest genetic determinant of late-onset AD, increasing risk in a gene dose-dependent manner, whereas APOE2 confers substantial protection.
“APOE4 is the strongest genetic determinant of late-onset AD, increasing risk in a gene dose-dependent manner, whereas APOE2 confers substantial protection 1 -5 .”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [2]
APOE4 carriers make up 55-75% of AD cases.
“As APOE4 carriers make up 55–75% of AD cases17–20”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [19]
Differences in APOE isoform-specific receptor binding affinity and lipid interactions affect neuroinflammation, tau pathology, and amyloid plaque dynamics.
“Studies indicate that APOE binding is integral to some of these processes [16–20] with differences in APOE isoform-specific receptor binding affinity and lipid interactions affecting neuroinflammation, tau pathology, and amyloid plaque dynamics [21–24].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [24]
APOE and APOE3Ch influence both Aβ and tau pathology, either directly or through downstream effects such as neuroinflammation.
“Collectively, these recent findings underscore the influence of APOE and APOE3Ch on both Aβ and tau pathology, either directly or through downstream effects such as neuroinflammation.”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [24]
Initial histopathological studies demonstrated a positive correlation between plaque density and apoE ε4 allele dose.
“Initial histopathological studies investigating the relationship between amyloid plaques and apoE isoforms demonstrated a positive correlation between plaque density and apoE ε4 allele dose (Rebeck et al., 1993; Schmechel et al., 1993).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Rebeck et al., 1993

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Authors: William Rebeck, G., Reiter, J. S., Strickland, D. K., & Hyman, B. T.
Affiliations: Massachusetts General Hospital (US)
American Red Cross (US)
ORCID: Strickland, Dudley K.
Hyman, Bradley T.
Venue: Neuron
Publisher: Elsevier BV
Published: 1993-10
Volume: 11
Issue: 4
Pages: 575-580
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/0896-6273(93)90070-8
OpenAlex: W2091924214
Cited by: 1,107
References: 7
Citations by year: 2026: 16 · 2025: 14 · 2024: 27 · 2023: 24 · 2022: 25 · 2021: 20 · 2020: 25 · 2019: 16 · 2018: 18 · 2017: 34 · 2016: 25 · 2015: 25 · 2014: 31 · 2013: 24 · 2012: 27
FWCI: 47.97
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01gm042581-09, 1f32ag005598-01)
National Institute on Aging (AG-08487, AG05598)
National Institute of General Medical Sciences (GM-42581)
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, Alzheimer's disease, APOE ε4, amyloid plaques, apoE receptors, LDL receptor, LDL receptor-related protein, astrocytes
MeSH terms: Adult, Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Genotype, Hippocampus, Humans, Immunohistochemistry, Middle Aged, Receptors, Immunologic, Receptors, LDL, Reference Values, Temporal Lobe, Genetic Variation, Low Density Lipoprotein Receptor-Related Protein-1

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Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions

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