Elsevier

Brain Research

Volume 755, Issue 2, 2 May 1997, Pages 193-201
Brain Research

Research report
Human choroid plexus is an uniquely involved area of the brain in amyloidosis: a histochemical, immunohistochemical and ultrastructural study

https://doi.org/10.1016/S0006-8993(97)00097-8Get rights and content

Abstract

To better understand the characteristics of amyloid deposition in the choroid plexus, we examined autopsied brain by routine histology, immunohistochemistry, and electron microscopy in three group of patients: primary systemic amyloidosis (n=7), cerebral amyloid angiopathy (CAA, n=6), and controls (n=3). Three of the CAA patients had Alzheimer's disease. Congophilic, birefringent amyloid deposits of the choroid plexus were seen in six of the seven cases of systemic light chain amyloidosis. Immunohistochemistry revealed that the deposited amyloids had reactivity for immunoglobulin light chain and amyloid P component. Accumulation of macrophages labeled with monoclonal antibodies against CD 68 and major histocompatibility complex class II antigens were observed around the massive amyloid deposits. The presence of approximately 10 nm amyloid fibrils along the epithelial basement membrane as well as in the vascular walls was ascertained by electron microscopy. In CAA, Congo red-positive amyloid deposits were consistently present in meningeal blood vessels and were often found in senile plaques of the cerebral parenchyma; congophilic amyloid deposits were absent in the choroid plexus. Choroid plexus epithelial cells exhibited immunostaining for beta amyloid precursor protein (APP) with N-terminal- and C-terminal-specific antibodies; in particular, consistent staining was obtained for the latter antibody. Immunoreactivity for amyloid β protein (Aβ) with monoclonal antibodies (6E10, 4G8) was often found in choroid plexus epithelial cells. These findings suggest that amyloid deposition of the choroid plexus depends on the major component protein in amyloidosis, and that the choroid plexus may produce APP and Aβ protein although Aβ amyloidosis is not evident in the choroid plexus. ©1997 Elsevier Science B.V. All rights reserved.

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.

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