FAMILIAL AMYLOID POLYNEUROPATHY ASSOCIATED WITH TRANSTHYRETIN GLY42 MUTATION - A QUANTITATIVE LIGHT AND ELECTRON-MICROSCOPIC STUDY OF THE PERIPHERAL NERVOUS-SYSTEM
K. Toyooka et al., FAMILIAL AMYLOID POLYNEUROPATHY ASSOCIATED WITH TRANSTHYRETIN GLY42 MUTATION - A QUANTITATIVE LIGHT AND ELECTRON-MICROSCOPIC STUDY OF THE PERIPHERAL NERVOUS-SYSTEM, Acta Neuropathologica, 90(5), 1995, pp. 516-525
We performed extensive quantitative analyses of the peripheral nervous
system (PNS) of two siblings with familial amyloid polyneuropathy (FA
P) caused by a transthyretin (TTR) Gly42 mutation. Pronounced amyloid
deposition was found in the sympathetic ganglia (SyG), dorsal root gan
glia (DRG) and throughout the length of the peripheral nerve fibers wi
th some accentuation in the more proximal portion. There was severe ne
uronal loss in the SyG and DRG together with nerve fiber depletion in
the nerve trunk, while only a small amount of amyloid deposition with
mild fiber loss was seen in the spinal roots. Sprouts of regenerating
axons were very scanty even in the spinal nerves or roots. A teased fi
ber study mainly showed demyelinating fibers, but axonal degeneration
was also present throughout peripheral nerves. An electron microscopic
study showed fine amyloid fibrils in direct contact with The axoplasm
ic membrane of demyelinated axons and destruction of axons in some are
as. Amyloid deposition within the PNS in this type of FAP resembled th
at in type I FAP (TTR Met30). However, direct axonal damage by amyloid
fibrils appeared to be more prominent in our cases than in type I FAP
. Lectin histochemistry using Ulex- europaeus agglutinin I demonstrate
d preferential depletion of small neurons in the DRG and their primary
afferent fibers in the spinal dorsal hem. Primary axonal degeneration
and ganglionopathy due to amyloid deposition appear to be the pathoge
netic mechanisms for peripheral neuropathy in this type of FAP.