Research reportHuman choroid plexus is an uniquely involved area of the brain in amyloidosis: a histochemical, immunohistochemical and ultrastructural study
Introduction
The choroid plexus is the specialized organ of the central nervous system (CNS) responsible for the production of cerebrospinal fluid (CSF). This organ lacks a blood-brain barrier (BBB). In systemic amyloidosis, amyloid deposition in the vessel walls and parenchyma of the CNS is rare 3, 13, 34. The blood vessels, however, of some exceptional BBB-free regions of the brain show amyloid deposition in systemic amyloidosis 7, 19, and the choroid plexus often shows prominent amyloid deposition [25]. In familial amyloidotic polyneuropathy, the choroid plexus is also one of the exceptional CNS areas showing consistent amyloid deposition [40].
Cerebral amyloid angiopathy (CAA) is characterized by amyloid deposits in the walls of brain blood vessels. Amyloid β protein (Aβ) is a major component of the amyloid responsible for the common sporadic form of CAA [46]. A soluble form of Aβ has already been described in the CSF in normal and diseased brains 36, 44. Recent studies showed that choroid plexus epithelial cells reacted positively for Aβ monoclonal antibody, 6E10, in Alzheimer's disease (AD) patients [6]and that, in immunoblotting experiments, the level of Aβ was increased in the choroid plexus obtained from AD subjects compared to age-matched controls [31]. So far, there has been no detailed immunohistochemical study of Aβ expression in the choroid plexus.
In this study, the characteristics of the choroid plexus in the CNS were compared among systemic amyloidosis, CAA including AD, and controls using histochemical, immunohistochemical and ultrastructural techniques. This study revealed unique patterns of amyloid deposition and the presence of amyloid protein in the choroid plexus in patients with systemic and localized amyloidosis.
Section snippets
Subjects
Samples were obtained at autopsy from seven patients (three females and four males; mean age=65 years) with systemic amyloidosis, six patients (two females and four males; mean age=66 years) with CAA, and three non-amyloidosis controls (three males; mean age=64 years). All cases of systemic amyloidosis were diagnosed as light chain amyloidosis (AL) by general pathology. The mean of the postmortem interval was 5, 9, and 3 h, respectively. Three patients in the CAA group were
Results
Table 2 summarizes the clinical characteristics and the degree of amyloid deposition in the brain of each patient.
Discussion
Our data showed that amyloid deposition in the choroid plexus occurred frequently (86%) in patients with systemic AL amyloidosis. The deposition of amyloid fibrils and the presence of amyloid protein (AL, AP) was confirmed by electron microscopy and immunohistochemistry. The presence of amyloid deposits in the choroid plexus appears to be due to the lack of a BBB, as previously demonstrated 26, 42. Our materials were limited to AL amyloidosis, but amyloid deposits have been shown in brain
Acknowledgements
We thank Masako Kohno and Kohji Isoda for their technical assistance.
References (48)
- Argiles, A., Mourad, G., Kerr, P.G., Garcia, M., Collins, B. and Demaille, J.G., Cells surrounding...
- Breathnach, S.M., Melrose, S.M., Bhogal, B., De Beer, F.C., Dyck, R.F., Tennent, G., Black, M.M. and Pepys, M.B.,...
- Briggs, G.W., Amyloidosis, Ann. Intern. Med., 55 (1961)...
- Castano, E.M. and Frangione, B., Human amyloidosis, Alzheimer's disease and related disorders, Lab. Invest., 58 (1988)...
- Cohen, A.S. and Connors, L.H., The pathogenesis and biochemistry of amyloidosis, J. Pathol., 151 (1987)...
- Cortez, S., Johanson, C., Kuo-LeBlanc, V., Rodriguez-Wolf, M., Baird, A., Gonzalez, A.M., Seddon, A., Bohlen, P. and...
- Diezel, P.B., Amyloide Strukturen im Nervensystem, Proc. IVth Int. Cong. Neuropathol, Georg Thieme, Stuttgart, 1 (1962)...
- Duston, M.A., Skinner, M., Anderson, J. and Cohen, A.S., Peripheral neuropathy as an early marker of AL amyloidosis,...
- Dyck, R.F., Evans, D.J., Lockwood, C.M., Rees, A.J., Turner, D. and Pepys, M.B., Amyloid P-component in human...
- Frackowiak, J., Zoltowska, A. and Wisniewski, H.W., Non-fibrillar β-amyloid protein is associated with smooth muscle...
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