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The precursor protein of non-Aβ component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system
Open accessAbstract
Non-A beta component of Alzheimer's disease amyloid (NAC) is the second component in the amyloid from brain tissue of patients affected with Alzheimer's disease. Its precursor protein (NACP) was shown to be a brain-specific protein. In rat brain, NACP was more abundant in the neocortex, hippocampus, olfactory bulb, striatum, thalamus, and cerebellum and less abundant in the brain stem. Confocal laser microscopy analysis revealed that anti-NACP immunostaining was colocalized with synaptophysin-immunoreactive presynaptic terminals. Ultrastructural analysis showed that NACP immunoreactivity was associated with synaptic vesicles. NACP sequence showed 95% identity with that of rat synuclein 1, a synaptic/nuclear protein previously identified in rat brain, and good homology with Torpedo synuclein from the electric organ synapse and bovine phosphoneuroprotein 14 (PNP-14), a brain-specific protein present in synapses. Therefore, NACP is a synaptic protein, suggesting that synaptic aberration observed in senile plaques might be involved in amyloidogenesis in Alzheimer's disease.
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“αSyn is predominantly expressed within the presynaptic terminals of neurons [141–143]”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [141]
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Metadata
- Authors
- Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., Rohan de Silva, H. A., Kittel, A., & Saitoh, T.
- Affiliations
- University of California San Diego (US)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1995-02
- Volume
- 14
- Issue
- 2
- Pages
- 467-475
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2059261643
- Cited by
- 1,316
- References
- 48
- Citations by year
- 2026: 21 · 2025: 23 · 2024: 34 · 2023: 36 · 2022: 60 · 2021: 56 · 2020: 69 · 2019: 59 · 2018: 62 · 2017: 49 · 2016: 53 · 2015: 61 · 2014: 52 · 2013: 41 · 2012: 47
- FWCI
- 12.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Health Assistance Foundation
- National Institutes of Health
- National Institute on Aging (AG10689, AG05131, R01AG010689, P50AG005131)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- presynaptic proteins, synaptic vesicles, synaptophysin, amyloidogenesis, amyloid plaques, brain distribution, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Animals, Antibodies, Antibody Specificity, Brain, Cattle, Humans, Molecular Sequence Data, Oligopeptides, Organ Specificity, Recombinant Proteins, Torpedo, Blotting, Western, Microscopy, Immunoelectron, Amyloid beta-Protein Precursor, Synaptophysin, Rats, Sprague-Dawley, Sequence Homology, Amino Acid, Microscopy, Confocal, Rats
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