The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Oligomerization of Alzheimer's β-Amyloid within Processes and Synapses of Cultured Neurons and Brain
Open accessAbstract
Multiple lines of evidence implicate β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD), but the mechanisms whereby Aβ is involved remain unclear. Addition of Aβ to the extracellular space can be neurotoxic. Intraneuronal Aβ42 accumulation is also associated with neurodegeneration. We reported previously that in Tg2576 amyloid precursor protein mutant transgenic mice, brain Aβ42 localized by immunoelectron microscopy to, and accumulated with aging in, the outer membranes of multivesicular bodies, especially in neuronal processes and synaptic compartments. We now demonstrate that primary neurons from Tg2576 mice recapitulate the in vivo localization and accumulation of Aβ42 with time in culture. Furthermore, we demonstrate that Aβ42 aggregates into oligomers within endosomal vesicles and along microtubules of neuronal processes, both in Tg2576 neurons with time in culture and in Tg2576 and human AD brain. These Aβ42 oligomer accumulations are associated with pathological alterations within processes and synaptic compartments in Tg2576 mouse and human AD brains.
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“Intraneuronal Ab is derived from Ab internalized by neurons from the extracellular space through ApoE-dependent and ApoE-independent uptakes and from intrinsic Ab that escapes exocytosis after APP cleavage that takes place in the endocytic compartment.34”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [34]
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In the citing paper
“Intraneuronal accumulation of Ab is a potentially important aspect of AD pathogenesis.”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [34]
In the citing paper
“a subsequent immuno-EM study demonstrated that intraneuronal accumulation of higher molecular weight Aβ42 oligomers (antibody M16; [210]) was invariably associated with neuritic degeneration, even prior to plaques, in vulnerable distal neurites and synaptic compartments in brains of AD transgenic mice and human AD [187].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [187]
In the citing paper
“C-terminal specific Aβ42 antibodies typically are best at detecting Aβ42 monomers, and have minimal reactivity against oligomers larger than trimers [187].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [187]
In the citing paper
“Emerging data, such as FAD mutations noted above, and the direct association of intraneuronal Aβ42 with subcellular pathology [187, 188], cell death [23, 167], and behavioral and physiological abnormalities, even prior to plaques, in AD transgenic mouse models [140], are providing increasing evidence for the importance of intraneuronal Aβ.”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [187]
In the citing paper
“Immuno-EM images of completely abnormal Aβ42 accumulating dystrophic neurites [187, 188], lacking the normal microtubule tracks required for organelle trafficking, secretion and exocytosis, argue against the active secretion of aggregating Aβ42 from neuritis prior to the dissolution of the plasma membrane [95].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [187]
In the citing paper
“It needs to be stressed again that by immuno-EM high molecular weight Aβ42 oligomers are consistently associated with pathology within neurites even prior to plaques [187].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [187]
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Citations
Cites
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Alzheimer's Disease: Genes, Proteins, and Therapy
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Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
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Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
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Receptor downregulation and multivesicular-body sorting
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Kawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00372.2001 · Cited by 1,053 · cited 1×
“A 42 oligomerization in Tg2576 mouse brain with aging A previous report showed that microdeposits of A 42 appear as early as 7– 8 months in Tg2576 brain (Kawarabayashi et al., 2001).”
MethodIntraneuronal Aβ42 Accumulation in Human Brain
Gouras, G. K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J. P., Haroutunian, V., Buxbaum, J. D., Xu, H., et al. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64700-1 · Cited by 991
Self-citation
Research works printed but not linked: 1
- Peters A, Palay SL, Webster Hd (1991) The fine structure of nervous system. Oxford: Oxford UP.
Cited by
Sorted by citations
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530
“Accumulation of intraneuronal A has been observed in the brains of AD (Gouras et al., 2000; Takahashi et al., 2002; Cataldo et al., 2004; Takahashi et al., 2004), Down’s syndrome (DS) (Gouras et al., 2000; Gyure et al., 2001; Busciglio et al., 2002; Mori et al., 2002; Cataldo et al., 2004), and AD…”
BackgroundIntracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561
Self-citationDeciphering the Molecular Basis of Memory Failure in Alzheimer's Disease
Walsh, D. M., & Selkoe, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.010 · Cited by 1,207
Classification and basic pathology of Alzheimer disease
Duyckaerts, C., Delatour, B., & Potier, M.-C. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0532-1 · Cited by 1,031
Metadata
- Authors
- Takahashi, R. H., Almeida, C. G., Kearney, P. F., Yu, F., Lin, M. T., Milner, T. A., & Gouras, G. K.
- Affiliations
- Cornell University (US)
- Corresponding author
- Gouras, Gunnar K.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-04-07
- Volume
- 24
- Issue
- 14
- Pages
- 3592-3599
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6729733
- OpenAlex
- W2128779293
- Cited by
- 445
- References
- 48
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 10 · 2023: 10 · 2022: 18 · 2021: 18 · 2020: 9 · 2019: 16 · 2018: 13 · 2017: 19 · 2016: 14 · 2015: 12 · 2014: 18 · 2013: 22 · 2012: 26
- FWCI
- 22.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- American Academy of Neurology
- National Institutes of Health (2k08ns002037-04, HL18974)
- National Heart, Lung, and Blood Institute (HL-18974, P01HL018974)
- National Institute of Neurological Disorders and Stroke (NS02037, R01NS045677, NS 045677)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, neural processes, synapses, multivesicular bodies, endosomal vesicles, microtubules, Tg2576 mice, amyloid precursor protein, neurodegeneration, primary neurons
- MeSH terms
- Adult, Aging, Alzheimer Disease, Animals, Brain, Cells, Cultured, Disease Models, Animal, Fluorescent Antibody Technique, Humans, Mice, Transgenic, Microtubules, Middle Aged, Neurons, Peptide Fragments, Endosomes, Synapses, Organelles, Amyloid beta-Peptides, Macromolecular Substances, Mice
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