Immunohistochemical Visualization of Amyloid-β Protein Precursor and Amyloid-β in Extra- and Intracellular Compartments in the Human Brain
Open accessAbstract
Amyloid-beta (Abeta) peptide, a cleavage product of the amyloid-beta protein precursor (AbetaPP), has been reported to be detected in the intracellular compartment. Most studies reporting the presence of intracellular Abeta are based on the use of immunohistochemistry. In this study, the presence of AbetaPP and Abeta was assessed by applying immunohistochemistry in postmortem human brain tissue samples obtained from 10 neurologically intact subjects, the youngest being 2 years of age, one aged with mild cognitive impairment, 14 neurologically diseased, and in one brain biopsy sample obtained from a subject with normal pressure hydrocephalus. Intracellular immunoreactivity was detected in all ages independent of the disease state or existence of extracellular Abeta aggregates with all antibodies directed to AbetaPP, with three Abeta antibodies (4G8, 6E10, and 82E1), clones that are unable to distinguish Abeta from AbetaPP. These results suggest that it is AbetaPP rather than Abeta that is detected intracellularly when using the antibodies listed above. Furthermore, the staining results varied when different pretreatment strategies were applied. Interestingly intracellular Abeta was detected with antibodies directed to the C-terminus of Abeta (neoepitope) in subjects with Alzheimer's disease. The lack of intracellular immunoreactivity in unimpaired subjects, when using antibodies against neoepitopes, may be due to a lack or a low level of the protein that is thus undetectable at light microscopic level by immunohistochemistry method. The staining results and conclusions depended strongly on the chosen antibody and the pretreatment strategy and thus multiple antibodies must be used when assessing the intracellular accumulation of Abeta.
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The discrepancy in intraneuronal Aβ levels in 3xTg mice might be due to APP cross-reacting antibodies such as 6E10 or 4G8, which detect central Aβ epitopes and also pick up full-length APP, resulting in overestimation of effective intraneuronal Aβ levels in the hippocampus.
“This discrepancy to the abovementioned data in models with intraneuronal Aβ accumulation might be due to the use of APP cross-reacting antibodies (such as 6E10 or 4G8), which have been frequently used for Aβ labelling [111]. As these antibodies detect central Aβ epitopes, they usually also pick-up considerable levels of full-length APP, resulting in an overestimation of the effective intraneuronal”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [111]
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“This discrepancy to the abovementioned data in models with intraneuronal Aβ accumulation might be due to the use of APP cross-reacting antibodies (such as 6E10 or 4G8), which have been frequently used for Aβ labelling [111].”
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- Authors
- Aho, L., Pikkarainen, M., Hiltunen, M., Leinonen, V., & Alafuzoff, I.
- Affiliations
- University of Eastern Finland (FI)
- Kuopio University Hospital (FI)
- Uppsala University (SE)
- Corresponding author
- Alafuzoff, Irina
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2010-06-13
- Volume
- 20
- Issue
- 4
- Pages
- 1015-1028
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1558118820
- Cited by
- 71
- References
- 57
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 10
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- European Commission (LSHM-CT-2004-503039)
- Academy of Finland (5772708)
- Suomen Kulttuurirahasto
- Kuopion Yliopistollinen Sairaala (5772708)
- 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
- amyloid-beta, amyloid precursor protein
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Antibodies, Biopsy, Brain Chemistry, Child, Child, Preschool, Cognition Disorders, Extracellular Space, Female, Humans, Immunohistochemistry, Infant, Middle Aged, Molecular Sequence Data, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Oligonucleotide Array Sequence Analysis, Intracellular Space, Young Adult
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