Familial amyloid polyneuropathy: a clinico-pathologic study.
In familial amyloid polyneuropathy (FAP), destruction of nerve fibres is related to accumulation of mutated transthyretin (mTTR) derived amyloid deposits (AD) in the endoneurium. Liver transplantation (LT), which removes the main source of mTTR, does not prevent deterioration of the clinical condition in all recipients.


METHODS
We evaluated the distribution of AD in the central and peripheral nervous system in order to better understand the pathophysiology of FAP and the potential role of lesions of nerve blood vessels and of mTTR released by choroid plexuses (CP). Forty nerve biopsy specimens and 3 autopsy cases, including 7 patients who underwent liver transplantation, all from patients with symptomatic FAP and DNA mutation of the TTR gene, were included.


RESULTS
Patients were ranged into three categories: MORPHOLOGICAL CHANGES: Amyloid predominated around endoneurial capillaries in 37 patients, with occlusion/destruction of endoneurial capillaries in 15 nerves at late stages of the disease. Post-mortem examination showed amyloid in choroid plexuses and perivascular spaces in the brain and around blood vessels penetrating the endoneurium, following arachnoid and connective tissue septae. Destruction of endoneurial blood vessels is a late event in the natural course of FAP. Morphological findings were similar in patients who underwent liver transplantation and in those who did not. The distribution of amyloid in areas communicating with the subarachnoid space suggests that mutated TTR released in the CSF may move to the endoneurial fluid and accumulate in peripheral nerves, accounting for lack of efficacy of liver transplantation in some individuals.
Said
Gérard
G
Fédération des Maladies Neurologiques-Hôpital de la Salpétrière-Assistance Publique Hôpitaux de Paris, France. dr-gs@hotmail.fr
Planté-Bordeneuve
Violaine
V
D000328:Adult; D000368:Aged; D000682:Amyloid / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D001706:Biopsy; D002831:Choroid Plexus / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008578:Meninges / Q000473:pathology; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure; D036421:Nerve Fibers, Unmyelinated / Q000648:ultrastructure; D010525:Peripheral Nerves / Q000098:blood supply / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D010543:Peroneal Nerve / Q000473:pathology; D017354:Point Mutation; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism; D013346:Subarachnoid Space
D000682:Amyloid; D011228:Prealbumin; C041120:amyloid prealbumin