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Transthyretin and Alzheimer's disease: where in the brain?
Neurobiol Aging. 2007 May; 28(5):713-8.NA

Abstract

Transthyretin (TTR), a carrier protein for thyroxine and retinol in plasma and cerebrospinal fluid (CSF), has been shown to bind the amyloid beta peptide. Accordingly, TTR has been suggested to protect against amyloid beta deposition, a key pathological feature in Alzheimer's disease (AD). Supporting this view are the reduced TTR levels found in CSF of patients with AD, as well as reports of altered TTR expression in the cortex and hippocampus of AD rodent models. Importantly, early characterization of TTR distribution revealed the choroid plexus as the site of TTR synthesis within the brain. To resolve this controversy we used precise laser microdissection technology to assay for TTR mRNA expression. Our results clearly demonstrate that TTR is not produced in the brain parenchyma of wild-type mice nor in two different transgenic mouse models of AD, suggesting that contamination by choroid plexus contributed to the recent results indicating TTR production in various brain regions. The relevance of TTR to AD should now take into consideration TTR production by the choroid plexus and its ability, in the CSF, to sequester the amyloid beta peptide.

Authors+Show Affiliations

Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16698124

Citation

Sousa, João Carlos, et al. "Transthyretin and Alzheimer's Disease: Where in the Brain?" Neurobiology of Aging, vol. 28, no. 5, 2007, pp. 713-8.
Sousa JC, Cardoso I, Marques F, et al. Transthyretin and Alzheimer's disease: where in the brain? Neurobiol Aging. 2007;28(5):713-8.
Sousa, J. C., Cardoso, I., Marques, F., Saraiva, M. J., & Palha, J. A. (2007). Transthyretin and Alzheimer's disease: where in the brain? Neurobiology of Aging, 28(5), 713-8.
Sousa JC, et al. Transthyretin and Alzheimer's Disease: Where in the Brain. Neurobiol Aging. 2007;28(5):713-8. PubMed PMID: 16698124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transthyretin and Alzheimer's disease: where in the brain? AU - Sousa,João Carlos, AU - Cardoso,Isabel, AU - Marques,Fernanda, AU - Saraiva,Maria João, AU - Palha,Joana Almeida, Y1 - 2006/05/15/ PY - 2005/08/12/received PY - 2006/03/24/revised PY - 2006/03/31/accepted PY - 2006/5/16/pubmed PY - 2007/6/1/medline PY - 2006/5/16/entrez SP - 713 EP - 8 JF - Neurobiology of aging JO - Neurobiol Aging VL - 28 IS - 5 N2 - Transthyretin (TTR), a carrier protein for thyroxine and retinol in plasma and cerebrospinal fluid (CSF), has been shown to bind the amyloid beta peptide. Accordingly, TTR has been suggested to protect against amyloid beta deposition, a key pathological feature in Alzheimer's disease (AD). Supporting this view are the reduced TTR levels found in CSF of patients with AD, as well as reports of altered TTR expression in the cortex and hippocampus of AD rodent models. Importantly, early characterization of TTR distribution revealed the choroid plexus as the site of TTR synthesis within the brain. To resolve this controversy we used precise laser microdissection technology to assay for TTR mRNA expression. Our results clearly demonstrate that TTR is not produced in the brain parenchyma of wild-type mice nor in two different transgenic mouse models of AD, suggesting that contamination by choroid plexus contributed to the recent results indicating TTR production in various brain regions. The relevance of TTR to AD should now take into consideration TTR production by the choroid plexus and its ability, in the CSF, to sequester the amyloid beta peptide. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/16698124/Transthyretin_and_Alzheimer's_disease:_where_in_the_brain L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(06)00109-6 DB - PRIME DP - Unbound Medicine ER -