title: Transthyretin and Alzheimer's disease: where in the brain?
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.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
authors.forename: João Carlos
authors.initials: JC
authors.lastname: Sousa
authors.forename: Isabel
authors.initials: I
authors.lastname: Cardoso
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Saraiva
authors.forename: Joana Almeida
authors.initials: JA
authors.lastname: Palha
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011228:Prealbumin / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D011228:Prealbumin