Distribution and progression of cerebral amyloid angiopathy in early-onset V30M (p.V50M) hereditary ATTR amyloidosis

Abstract

Background

Cerebral amyloid angiopathy (CAA) is becoming the most common and serious complications in long-lived hereditary ATTR amyloidosis patients. It is therefore imperative to elucidate the characteristics of ATTR-type CAA and develop useful biomarkers.

Methods

We enrolled 34 ATTRv amyloidosis patients with the V30M (p.V50M) variant for analysis with three-dimensional stereotactic surface projection z score imaging of Pittsburgh compound B (PiB)-PET.

Results

Eight patients exhibited central nervous system (CNS) symptoms. Seven patients suffered transient focal neurologic episodes, and 2 patients each experienced cerebellar haemorrhages or cognitive decline. The amount of ¹¹C-PiB accumulation increased as a function of disease duration. ¹¹C-PiB-PET abnormalities were seen at 8 years from onset and were associated with CNS manifestations from 12 years. The annual increase rate of the standardised uptake value ratio (SUVR) in female patients was significantly higher than in male patients. CNS amyloid deposition started in the upper middle surface of the cerebellar cortex, and then spread out over the entire surface of the cerebellum, Sylvian fissure, and anterior part of the longitudinal fissure of the cerebrum.

Conclusions

PiB-PET is a useful biomarker for the early detection and treatment evaluation of ATTR-type CAA. Female gender is associated with more rapid progression of ATTR-type CAA.

Keywords:

• Cerebral amyloid angiopathy
• Pittsburgh compound B
• positron emission tomography
• hereditary ATTR amyloidosis
• transthyretin

Acknowledgments

The authors thank Mr. Hirofumi Kawakami of GE Healthcare Japan for his support in the 3D-SSP analysis of ¹¹C-PiB-PET imaging.

Disclosure statement

Dr. Yoshiki Sekijima has received honoraria and research grants from Pfizer and Alnylam Pharmaceuticals.

Additional information

Funding

This study was supported by a Grant-in-aid for Scientific Research [19K07959 to Y.S.] and a grant from the Amyloidosis Research Committee (20FC1022), the Ministry of Health, Labour and Welfare, Japan.