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06:33
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Familial amyloid polyneuropathy: a clinico-pathologic study.
Gérard Said1, Violaine Planté-Bordeneuve
1Fédération des Maladies Neurologiques-Hôpital de la Salpétrière-Assistance Publique Hôpitaux de Paris, France. dr-gs@hotmail.fr
Journal of the Neurological Sciences
|May 27, 2009
Summary
Familial amyloid polyneuropathy (FAP) involves nerve fiber destruction from mutated transthyretin amyloid deposits. Even after liver transplants, amyloid accumulation persists in some patients, suggesting alternative pathways of disease progression.
Area of Science:
- Neurology
- Pathology
- Genetics
Background:
- Familial amyloid polyneuropathy (FAP) is characterized by nerve fiber damage due to mutated transthyretin (mTTR) amyloid deposits (AD) in the endoneurium.
- Liver transplantation (LT) aims to reduce mTTR, the primary source, but clinical improvement is not universal.
Purpose of the Study:
- To investigate the distribution of AD in the central and peripheral nervous systems.
- To understand FAP pathophysiology, including the role of nerve blood vessel lesions and mTTR from choroid plexuses (CP).
Main Methods:
- Analysis of 40 nerve biopsy specimens and 3 autopsy cases from symptomatic FAP patients with TTR gene mutations.
- Inclusion of 7 patients who had undergone liver transplantation.
Main Results:
- Amyloid deposits were predominantly found around endoneurial capillaries, with capillary occlusion in advanced stages.
- Post-mortem findings revealed amyloid in choroid plexuses and brain perivascular spaces, and around penetrating blood vessels.
- Morphological changes were similar in transplanted and non-transplanted patients.
Conclusions:
- Destruction of endoneurial blood vessels is a late-stage FAP event.
- Amyloid distribution suggests mTTR from cerebrospinal fluid (CSF) may reach peripheral nerves via CSF-communicating spaces.
- This pathway may explain the limited efficacy of liver transplantation in some FAP patients.
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