Understanding the debilitating nature of the disease
SYSTEMIC
ATTR amyloidosis is characterised by the deposition of transthyretin (TTR) amyloid fibrils in various organs and tissues resulting in multisystem dysfunction1,3–6
PROGRESSIVE
Disease progression is associated with significant disability and poor quality of life7–13
POTENTIALLY FATAL
The disease is marked by substantial morbidity and has a poor prognosis.14–17 For patients with ATTRv-PN, median survival from diagnosis can range from 5–15 years14
ATTR amyloidosis is a protein-misfolding disease of the transthyretin (TTR) protein1
THE SOURCE OF THE DISEASE IS PRODUCED IN THE LIVER3,18
Liver
(where 90% of TTR is produced)
Transthyretin
tetramer destabilises
tetramer destabilises
Tetramer dissociates into monomers
Monomers misfold
and aggregate into amyloid fibrils
and aggregate into amyloid fibrils
Amyloid deposits throughout the body
Watch this video to learn more about the disease mechanism of ATTR amyloidosis
The disease is classified as hereditary or wild type18
Hereditary ATTR (ATTRv):
Instability of TTR is due to mutations in the TTR gene1,18
Wild-type ATTR (ATTRwt):
Instability of TTR may be due to age-related and other unknown factors18
UNDERSTAND MORE ABOUT THE DIFFERENCES BETWEEN HEREDITARY AND WILD-TYPE
- Age of onset is typically >30 years19
- Symptoms manifest as polyneuropathy (PN), cardiomyopathy (CM) or both1
- Patients are typically aged >60 years and male20
- Symptoms generally manifest as CM1
Mutations associated with ATTRv amyloidosis
- The most common TTR mutations in the UK and Ireland are T80A, V142I, and V50M21
- The V142I mutation is predominantly linked to cardiac manifestations; autonomic dysfunction and peripheral neuropathy are clinically rare8, 20–22
- The T80A mutation typically exhibits a mixed clinical phenotype, encompassing both cardiac and neuropathic features20,21
- The V50M mutation is predominantly associated with neuropathic features, though phenotypic penetrance is dependent on age as late-onset ATTRv amyloidosis with V50M mutation typically manifests as cardiomyopathy23
- In the UK, there are an estimated 230 people with ATTRv amyloidosis24
- It has been shown that around 1 in 1000 people in the UK carry likely pathogenic TTR variants, suggesting ATTRv amyloidosis may be more prevalent than currently estimated25
Patients are often defined by PN or CM presentation. In the UK, up to 29% of patients with ATTRv amyloidosis and up to 8% with ATTRwt amyloidosis have mixed presentation26
Transthyretin amyloidosis with polyneuropathy (ATTR-PN) is defined as patients presenting with manifestations that predominantly affect the peripheral nerves18
Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is defined as patients presenting with manifestations that predominantly affect the heart1,27
It is important to suspect ATTR amyloidosis signs and symptoms to facilitate earlier diagnosis and treatment1
Timely diagnosis and treatment of ATTR amyloidosis may help to improve patient outcomes28
GB-77259 I August 2026
