Transthyretin and the brain re-visited: Is neuronal synthesis of transthyretin protective in Alzheimer's disease?
<p>Abstract</p> <p>Since the mid-1990's a trickle of publications from scattered independent laboratories have presented data suggesting that the systemic amyloid precursor transthyretin (TTR) could interact with the amyloidogenic β-amyloid (Aβ) peptide of Alzheimer's dis...
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| Format: | Article |
| Language: | English |
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BMC
2011-11-01
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| Series: | Molecular Neurodegeneration |
| Subjects: | |
| Online Access: | http://www.molecularneurodegeneration.com/content/6/1/79 |
| _version_ | 1811278684966879232 |
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| author | Li Xinyi Buxbaum Joel N |
| author_facet | Li Xinyi Buxbaum Joel N |
| author_sort | Li Xinyi |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Since the mid-1990's a trickle of publications from scattered independent laboratories have presented data suggesting that the systemic amyloid precursor transthyretin (TTR) could interact with the amyloidogenic β-amyloid (Aβ) peptide of Alzheimer's disease (AD). The notion that one amyloid precursor could actually inhibit amyloid fibril formation by another seemed quite far-fetched. Further it seemed clear that within the CNS, TTR was only produced in choroid plexus epithelial cells, not in neurons. The most enthusiastic of the authors proclaimed that TTR sequestered Aβ <it>in vivo </it>resulting in a lowered TTR level in the cerebrospinal fluid (CSF) of AD patients and that the relationship was salutary. More circumspect investigators merely showed <it>in vitro </it>interaction between the two molecules. A single <it>in vivo </it>study in <it>Caenorhabditis elegans </it>suggested that wild type human TTR could suppress the abnormalities seen when Aβ was expressed in the muscle cells of the worm. Subsequent studies in human Aβ transgenic mice, including those from our laboratory, also suggested that the interaction reduced the Aβ deposition phenotype. We have reviewed the literature analyzing the relationship including recent data examining potential mechanisms that could explain the effect. We have proposed a model which is consistent with most of the published data and current notions of AD pathogenesis and can serve as a hypothesis which can be tested.</p> |
| first_indexed | 2024-04-13T00:40:14Z |
| format | Article |
| id | doaj.art-cf64bb0a40214a68928ff16ede135c12 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-04-13T00:40:14Z |
| publishDate | 2011-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-cf64bb0a40214a68928ff16ede135c122022-12-22T03:10:13ZengBMCMolecular Neurodegeneration1750-13262011-11-01617910.1186/1750-1326-6-79Transthyretin and the brain re-visited: Is neuronal synthesis of transthyretin protective in Alzheimer's disease?Li XinyiBuxbaum Joel N<p>Abstract</p> <p>Since the mid-1990's a trickle of publications from scattered independent laboratories have presented data suggesting that the systemic amyloid precursor transthyretin (TTR) could interact with the amyloidogenic β-amyloid (Aβ) peptide of Alzheimer's disease (AD). The notion that one amyloid precursor could actually inhibit amyloid fibril formation by another seemed quite far-fetched. Further it seemed clear that within the CNS, TTR was only produced in choroid plexus epithelial cells, not in neurons. The most enthusiastic of the authors proclaimed that TTR sequestered Aβ <it>in vivo </it>resulting in a lowered TTR level in the cerebrospinal fluid (CSF) of AD patients and that the relationship was salutary. More circumspect investigators merely showed <it>in vitro </it>interaction between the two molecules. A single <it>in vivo </it>study in <it>Caenorhabditis elegans </it>suggested that wild type human TTR could suppress the abnormalities seen when Aβ was expressed in the muscle cells of the worm. Subsequent studies in human Aβ transgenic mice, including those from our laboratory, also suggested that the interaction reduced the Aβ deposition phenotype. We have reviewed the literature analyzing the relationship including recent data examining potential mechanisms that could explain the effect. We have proposed a model which is consistent with most of the published data and current notions of AD pathogenesis and can serve as a hypothesis which can be tested.</p>http://www.molecularneurodegeneration.com/content/6/1/79Beta-amyloid precursor protein (AβPP, APP)Beta-amyloid (Aβ)Alzheimer's disease (AD)Transthyretin (TTR)AmyloidosisProtein homeostasisAggregation |
| spellingShingle | Li Xinyi Buxbaum Joel N Transthyretin and the brain re-visited: Is neuronal synthesis of transthyretin protective in Alzheimer's disease? Molecular Neurodegeneration Beta-amyloid precursor protein (AβPP, APP) Beta-amyloid (Aβ) Alzheimer's disease (AD) Transthyretin (TTR) Amyloidosis Protein homeostasis Aggregation |
| title | Transthyretin and the brain re-visited: Is neuronal synthesis of transthyretin protective in Alzheimer's disease? |
| title_full | Transthyretin and the brain re-visited: Is neuronal synthesis of transthyretin protective in Alzheimer's disease? |
| title_fullStr | Transthyretin and the brain re-visited: Is neuronal synthesis of transthyretin protective in Alzheimer's disease? |
| title_full_unstemmed | Transthyretin and the brain re-visited: Is neuronal synthesis of transthyretin protective in Alzheimer's disease? |
| title_short | Transthyretin and the brain re-visited: Is neuronal synthesis of transthyretin protective in Alzheimer's disease? |
| title_sort | transthyretin and the brain re visited is neuronal synthesis of transthyretin protective in alzheimer s disease |
| topic | Beta-amyloid precursor protein (AβPP, APP) Beta-amyloid (Aβ) Alzheimer's disease (AD) Transthyretin (TTR) Amyloidosis Protein homeostasis Aggregation |
| url | http://www.molecularneurodegeneration.com/content/6/1/79 |
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