Genetic studies support a neuronal origin for the beta amyloid polypeptide

Topic: Brain proteins, microglia and lab models

Studies of Alzheimer amyloid protein precursor mRNA expression in the human brain have provided compelling evidence for a neural origin of beta amyloid. Significant alterations in levels of amyloid precursor mRNAs are observed specifically in neurons known to be risk in Alzheimer's disease and Down syndrome. These data raise the possibility that an increase in the transcripts containing the protease inhibitor domain relative to the shorter transcript may account for the accumulation of beta amyloid.

Key findings

• Significant alterations in levels of amyloid precursor mRNAs are observed specifically in neurons known to be risk in Alzheimer's disease and Down syndrome.

Why it matters

This early work found altered levels of amyloid precursor mRNA specifically in neurons at risk in Alzheimer's disease and Down syndrome, suggesting a neuronal source of beta amyloid. It raises the possibility that a shift toward the transcript containing the protease inhibitor domain may explain beta amyloid accumulation, but no treatment or prevention is tested here.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/0197-4580(89)90074-2
• PubMed: 2510036
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{neve1989-2510036,
  author  = {Neve, R. L.},
  title   = {{Genetic studies support a neuronal origin for the beta amyloid polypeptide}},
  journal = {Neurobiology of aging},
  year    = {1989},
  doi     = {10.1016/0197-4580(89)90074-2},
  pmid    = {2510036},
  url     = {https://doi.org/10.1016/0197-4580(89)90074-2}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor Nature · 1987-02-01 · usefulness score 58/100 · Disease mechanisms
• Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus Science (New York, N.Y.) · 1987-02-01 · usefulness score 57/100 · Down syndrome and Alzheimer's
• Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides Proceedings of the National Academy of Sciences of the United States of America · 1987-06-01 · usefulness score 45/100 · Down syndrome and Alzheimer's

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• Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells The Journal of biological chemistry · 2009-06-19 · usefulness score 42/100
• The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid beta-protein gene Nature · 1987-09-01 · usefulness score 41/100
• beta-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer's disease Trends in neurosciences · 1993-10-01 · usefulness score 36/100
• Neuronal loss and beta-amyloid removal in the amygdala of people with Down syndrome Neurobiology of aging · 1999-05-01 · usefulness score 34/100
• The Amyloid Cascade Hypothesis: A Conclusion in Search of Support The American journal of pathology · 2024-11-10 · usefulness score 46/100
• The amyloid percursor protein of Alzheimer disease is expressed as a 130 kDa polypeptide in various cultured cell types FEBS letters · 1988-12-01 · usefulness score 37/100

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• A review that covers this ground Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice: a role for intraneuronal amyloid Neuroscience and biobehavioral reviews · 2006-10-20 · usefulness score 36/100
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