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A 47-year-old man presented with 2 years of cardiovascular autonomic failure and mild peripheral neuropathy. His father had CNS/leptomeningeal amyloidosis manifesting as hydrocephalus.He was confirmed to have Gly53Ala (heterozygous) ATTRv amyloidosis and commenced on patisiran.Subsequently, while investigating a transient focal neurological episode, his MRI brain showed a small volume of old subarachnoid haemorrhage in the posterior fossa. His CSF demonstrated an elevated CSF protein (1.37g/L) and neurofilament (1752pg/mL). CSF beta-amyloid 1-42/1-40 ratio was normal. Fluorbetaben-PET scan and electroencephalography was normal.He was diagnosed with early CNS amyloidosis. Given studies suggest tafamidis crosses the blood-brain-barrier in small amounts,1 261mg tafamidis daily was added to his patisiran on compassionate grounds.The patient remained clinically/radiographically stable for the following 30 months.However, serial CSF protein remained elevated and neurofilament steadily increased to 4220mg/mL. MRI brain at 30 months confirmed new leptomeningeal enhancement.Our case demonstrates CSF neurofilament maybe a potential marker for early CNS amyloidosis progression and that, in our patient with Gly53Ala ATTRv amyloidosis, 61mg tafamidis therapy may not prevent CNS progression. He is planned to be commenced on tolcapone – a possible CNS amyloid aggregate inhibitor. Treatment options for CNS manifestations of ATTRv amyloidosis requires further research.References Monteiro Cecilia, et al. Cerebrospinal fluid and vitreous body exposure to orally administered tafamidis in hereditary ATTRV30M(p. TTRV50M) amyloidosis patients. Amyloid 2018;25(2):120–128.Tsai Felix J, et al. Tafamidis concentration required for transthyretin stabilisation in cerebrospinal fluid. Amyloid 2023;30(3):279–289.victorzhang93@gmail.com