**1. Introduction**

Systemic amyloidosis comprises a group of diseases characterized by deposition of misfolded proteins which express abnormal β-sheet conformation usually in the extracellular spaces in different tissues [1]. At least 36 amyloid precursor proteins are recognized so far in the humans [2]. There are several general pathogenetic pathways that proteins become misfolded and create amyloid fibrils [3]: (1) presence of abnormal protein such as amyloid light chain (AL) or those caused by a mutation (such as familial ATTR and amyloidosis related to gelsolin mutations), (2) prolonged exposure to a normal protein such as systemic reactive (AA) and dialysis related amyloidosis; and (3) age related amyloidosis such as senile systemic amyloidosis. This book chapter will discuss the neurological manifestations of familial and wild-type ATTR, their diagnosis and treatment. Although neuropathy related to familial ATTR is uncommon, it is underdiagnosed and causes profound disability and mortality, largely as a result of concomitant cardiomyopathy. Timely diagnosis and treatment improves the outcome as new disease modifying treatments have become available.
