Relationship between apolipoprotein E and the amyloid deposits and dystrophic neurites of Alzheimer’s disease.
Open accessAbstract
Although the inheritance of certain apolipoprotein E (ApoE) alleles has been recognized as a genetic risk factor for Alzheimer's disease, the role of ApoE in the pathology underlying this disease is unclear. Several reports have emphasized the association of ApoE with either beta-amyloid plaque formation or the development of neurofibrillary pathology. Utilization of multiple label immunohistochemical methods enabled us to examine directly the localization of ApoE immunoreactivity relative to beta-amyloid plaques, dystrophic neurites and neurofibrillary tangles. In Alzheimer's disease cases, beta-amyloid plaques showing high ApoE immunoreactivity were localized to layers II, III and V of the neocortex. In layer I, beta-amyloid plaques were unlabelled for ApoE relative to beta-amyloid. Dense core plaques labelled for beta-amyloid often had only the central portions labelled for ApoE. Conversely, ApoE labelled spherical structures within some plaques were not immunoreactive for beta-amyloid or dystrophic neurite markers. Unlike beta-amyloid labelled plaques, all ApoE immunoreactive plaques were associated with dystrophic neurites. In preclinical Alzheimer's disease cases, most plaques were double labelled for beta-amyloid and ApoE. ApoE did not label dystrophic neurites or the early stages of neurofibrillary tangle formation, indicating that ApoE may not be directly involved in neurofibrillary pathology. The specific presence of ApoE in plaques associated with dystrophic neurites in demented patients suggests that ApoE may contribute toward a higher degree of beta-amyloid fibrillogenesis, enhancing the ability of certain plaques to cause damage to surrounding axons.
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Compared with cortical amyloid-β plaque, the density and distribution of phosphorylated tau aggregated in neurofibrillary tangles correlate more closely with Alzheimer disease-associated cognitive impairment and neurodegeneration.
“Compared with cortical Aβ plaque, the density and distribution of phosphorylated tau aggregated in NFTs correlate more closely with AD-associated cognitive impairment and neurodegeneration.12,13,14”
From Positron Emission Tomography Imaging With [ <sup>18</sup> F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [12]
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- Authors
- Dickson, T. C., Saunders, H. L., & Vickers, J. C.
- Affiliations
- University of Tasmania (AU)
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 1997-12
- Volume
- 23
- Issue
- 6
- Pages
- 483-491
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W2051348240
- Cited by
- 40
- References
- 31
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- 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, amyloid plaques, dystrophic neurites, neurofibrillary tangles, preclinical Alzheimer's disease, amyloid fibril formation, neocortex, genetic risk factors
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Frontal Lobe, Humans, Immunohistochemistry, Middle Aged, Temporal Lobe, Ubiquitins, Amyloid beta-Peptides, Neurites, Neurofibrillary Tangles, tau Proteins, Fluorescent Antibody Technique, Indirect, Plaque, Amyloid
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