Cited by 108Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Intracellular Accumulation of Insoluble, Newly Synthesized Aβn-42 in Amyloid Precursor Protein-transfected Cells That Have Been Treated with Aβ1–42

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Yang, Austin J., Chandswangbhuvana, Dhusdee, Shu, Theo, Henschen, Agnes, Glabe, Charles G.·1999·Journal of Biological Chemistry

Abstract

Our early study indicates that intracellular Abeta1-42 aggregates are resistant to degradation and accumulate as an insoluble residue in lysosomes, where they alter the normal catabolism of amyloid precursor protein (APP) to cause the accumulation of insoluble APP and amyloidogenic fragments. In this study, we examined whether the addition of exogenous Abeta1-42 also leads to the accumulation of newly synthesized intracellular Abeta. Here we describe that newly synthesized Abeta, especially Abetan-42, is generated from metabolically labeled APP and accumulates in the insoluble fraction of cell lysates after Abeta1-42 treatment. These results suggest that intracellular Abeta may derive from a solid phase, intracellular pathway. In contrast to the pathway that primarily produces secreted Abeta1-40, the solid-phase intracellular pathway preferentially produces Abetan-42 with ragged amino termini. Biochemical studies and amino acid sequencing analyses indicate that these intracellular Abeta also share the same types of Abeta structures that accumulate in the brain of Alzheimer's disease patients, suggesting that a significant fraction of the amyloid deposits in Alzheimer's disease may arise by this solid-phase pathway.

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Authors
Yang, A. J., Chandswangbhuvana, D., Shu, T., Henschen, A., & Glabe, C. G.
Affiliations
  • Nathan Kline Institute for Psychiatric Research (US)
  • University of California, Irvine (US)
Corresponding author
Yang, Austin J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1999-07
Volume
274
Issue
29
Pages
20650-20656
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2037197109
Cited by
108
References
39
Citations by year
2026: 1 · 2025: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 1 · 2013: 5 · 2012: 10
FWCI
6.61
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Alzheimer's Association
  • National Institutes of Health (AG00538)
  • National Institute on Aging (AG 00538)
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 42, amyloid precursor protein
MeSH terms
Alzheimer Disease, Autoradiography, Cells, Cultured, Chromatography, Gel, Chromatography, High Pressure Liquid, Peptide Fragments, Precipitin Tests, Transfection, Amyloid beta-Peptides, Amyloid beta-Protein Precursor

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