Aβ‐peptide length aid apolipoprotein E genotype in Alzheimer's disease
Abstract
Apolipoprotein ∈ (ApoE)ε4 allele, a risk factor for the development of Alzheimer's disease (AD), is associated with increased amyloid deposition. We examined cerebral cortex in 68 AD cases using antibodies to βbeta;‐amyloid (Aβbeta;) peptides of different length (Aβbeta;1−40 and Aβbeta;l−42) and found that the increased plaque frequency observed with ε4 genotypes may be largely attributed to an increase in Aβbeta;1−40‐positive plaques. Indeed, both the number of Aβbeta;1−40‐positive plaques, as well as the ratio of Aβbeta;I−40/ Aβbeta;1−42‐positive plaques, increased with ε4 dosage. In contrast, the frequency of Aβbeta;1−42‐immunoreactive plaques was similar for ε3/ε3,ε3/ε4 and ε4/ε4 genotypes. ApoE may influence Aβbeta; length by facilitating Aβbeta; 1−40 deposition onto Aβbeta;1−42‐seeded plaques or by modulating the activity of a putative carboxypeptidase that forms Aβbeta;1−40 from Aβbeta;1−42 in situ.
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Increased CAA in ε4-positive subjects does not entirely account for the preferential Aβ40 deposition.
“Although the apparent differential effects on Aβ40 and Aβ42 aggregation by apoE4 might be simply attributed to the increased CAA in apoε4 subjects, careful immunohistochemical analyses of plaques using Aβ40 or Aβ42 specific antibodies suggest that increased CAA in ε4-positive subjects does not entirely account for the preferential Aβ40 deposition (Gearing et al., 1996; Mann et al., 1997).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Gearing et al., 1996
Several reports suggest that Aβ40 preferentially aggregates in an apoE4 gene dose-dependent manner in AD subjects.
“Interestingly, there have been several reports suggesting that Aβ40 preferentially aggregates in an apoE4 gene dose-dependent manner in AD subjects (Gearing et al., 1996; Ishii et al., 1997; Mann et al., 1997).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Gearing et al., 1996
Cites
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H. (1994) · Nature · doi:10.1038/372092a0 · Cited by 871 · see citing works
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Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · 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
Berg, L., McKeel, D. W., Miller, J. P., Storandt, M., Rubin, E. H., Morris, J. C., Baty, J., Coats, M., Norton, J., Goate, A. M., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.3.326 · Cited by 657 · see citing works
Self-citationBales, K. R., Verina, T., Cummins, D. J., Du, Y., Dodel, R. C., Saura, J., Fishman, C. E., DeLong, C. A., Piccardo, P., Petegnief, V., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15233 · Cited by 486 · see citing works
Apolipoprotein E ε4 allele, AD pathology, and the clinical expression of Alzheimer’s disease
Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Aggarwal, N. T., Arnold, S. E., Cochran, E. J., Berry-Kravis, E., & Bienias, J. L. (2003) · Neurology · doi:10.1212/01.wnl.0000042478.08543.f7 · Cited by 282 · see citing works
Ling, Y., Morgan, K., & Kalsheker, N. (2003) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(03)00133-x · Cited by 224 · see citing works
Buttini, M., Yu, G.-Q., Shockley, K., Huang, Y., Jones, B., Masliah, E., Mallory, M., Yeo, T., Longo, F. M., & Mucke, L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-24-10539.2002 · Cited by 183 · see citing works
“…in their effects on A deposition (E4 E3) (Rebeck et al., 1993; Schmechel et al., 1993; Berr et al., 1994; Heinonen et al., 1995; Hyman et al., 1995; Gearing et al., 1996; Ishii et al., 1997; Johnson et al., 1998; McNamara et al., 1998; Holtzman et al., 2000a,b) but also in their capacity to…”
BackgroundMann, D. M. A., Pickering-Brown, S. M., Takeuchi, A., & Iwatsubo, T. (2001) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64688-3 · Cited by 182 · see citing works
Kuo, Y.-M., Kokjohn, T. A., Watson, M. D., Woods, A. S., Cotter, R. J., Sue, L. I., Kalback, W. M., Emmerling, M. R., Beach, T. G., & Roher, A. E. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64947-4 · Cited by 167 · see citing works
β-Amyloid (Aβ) Deposition in the Brains of Aged Orangutans
Gearing, M., Tigges, J., Mori, H., & Mirra, S. S. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00012-2 · Cited by 130 · see citing works
Self-citationMorishima-Kawashima, M., Oshima, N., Ogata, H., Yamaguchi, H., Yoshimura, M., Sugihara, S., & Ihara, Y. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64847-x · Cited by 119 · see citing works
Shinohara, M., Fujioka, S., Murray, M. E., Wojtas, A., Baker, M., Rovelet-Lecrux, A., Rademakers, R., Das, P., Parisi, J. E., Graff-Radford, N. R., et al. (2014) · Brain · doi:10.1093/brain/awu046 · Cited by 115 · see citing works
Appearance of Sodium Dodecyl Sulfate-Stable Amyloid β-Protein (Aβ) Dimer in the Cortex During Aging
Enya, M., Morishima-Kawashima, M., Yoshimura, M., Shinkai, Y., Kusui, K., Khan, K., Games, D., Schenk, D., Sugihara, S., Yamaguchi, H., et al. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65273-x · Cited by 111 · see citing works
Distinct Pools of β-Amyloid in Alzheimer Disease–Affected Brain: A Clinicopathologic Study
Steinerman, J. R., Irizarry, M., Scarmeas, N., Raju, S., Brandt, J., Albert, M., Blacker, D., Hyman, B., & Stern, Y. (2008) · Archives of Neurology · doi:10.1001/archneur.65.7.906 · Cited by 104 · see citing works
Mann, D. M. A., Davidson, Y. S., Robinson, A. C., Allen, N., Hashimoto, T., Richardson, A., Jones, M., Snowden, J. S., Pendleton, N., Potier, M.-C., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1866-3 · Cited by 73 · see citing works
Tian, J. (2004) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.012096 · Cited by 39 · see citing works
Development of amyloid burden in African Green monkeys
Kalinin, S., Willard, S. L., Shively, C. A., Kaplan, J. R., Register, T. C., Jorgensen, M. J., Polak, P. E., Rubinstein, I., & Feinstein, D. L. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.03.023 · Cited by 32 · see citing works
- Authors
- Gearing, M., Mori, H., & Mirra, S. S.
- Affiliations
- Atlanta VA Medical Center (US)
- Tokyo Institute of Psychiatry (JP)
- Emory University (US)
- Corresponding author
- Mirra, Suzanne S.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1996-03
- Volume
- 39
- Issue
- 3
- Pages
- 395-399
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2045471895
- Cited by
- 120
- References
- 2
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 4
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- 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
- Alzheimer's disease, APOE ε4, amyloid-beta, Aβ40, amyloid-beta 42, amyloid plaques, cerebral cortex, APOE genotype, carboxypeptidase, amyloid deposition
- MeSH terms
- Alzheimer Disease, Apolipoproteins E, Carboxypeptidases, Cerebral Cortex, Genotype, Humans, Immunohistochemistry, Amyloid beta-Peptides
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