An Exploratory Study of Cognitive Involvement in Hereditary Transthyretin Amyloidosis.

Abstract

Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis is an autosomal dominant disorder caused by mutations of the transthyretin (TTR) gene. The mutant ATTRv protein causes a systemic accumulation of amyloid fibrils in various organs. TTR is an important protein in the central nervous system physiology for the maintenance of normal cognitive process during aging, amidated neuropeptide processing, and nerve regeneration. The neuroprotective effect of transthyretin has been widely documented in animal models. Cognitive consequences of the mutant TTR in hereditary ATTRv amyloidosis patients remain still to be elucidated. We designed this study to investigate the cognitive involvement in ATTRv amyloidosis. Detailed neuropsychological tests and cranial MRIs were performed. Biomarkers including amyloid beta 1-42, total tau, and phosphorylated tau were investigated in the cerebrospinal fluid samples. Median age of the cohort was 52years (ranges 34-72). Neuropsychological assessment results were compatible with impaired executive functions (in all patients except one with only bilateral carpal tunnel syndrome, long-term visual and long-term verbal memory (severe in four patients and moderate in one). Visuospatial judgment and perception were impaired in six. Mean cerebrospinal fluid Aβ1-42 (pg/ml) was 878.0±249.5 in patients with cortical atrophyin MRI whereas 1210.0±45.9 in patients without any cortical atrophy. Cranial MRI showed cortical atrophy in six patients (6/10). Our data showed the significance of the TTR protein in cognitive functions and highlighted the importance of the close follow-up of cognitive functions in ATTRv amyloidosis patients.