Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val30Met familial amyloid polyneuropathy.

Abstract

Late-onset transthyretin Val30Met-associated familial amyloid polyneuropathy (FAP ATTR Val30Met) cases unrelated to endemic foci in Japan show different clinicopathological features from the conventional early-onset cases in endemic foci. We compared the characteristics of amyloid deposits in early-onset FAP ATTR Val30Met cases in endemic foci and late-onset cases in non-endemic areas. Amyloid deposits in three early-onset cases from endemic foci and five late-onset cases from non-endemic areas were systematically examined post-mortem. Amyloid deposits in early-onset cases were highly congophilic and showed strong apple-green birefringence with Congo red staining and had long, parallel fibrils in most organs. On the other hand, those in late-onset cases were generally weakly congophilic and showed faint apple-green birefringence with Congo red staining and had short, haphazard fibrils. In the renal glomus and adrenal gland of early-onset cases, the characteristics of amyloid deposits were similar to those observed in late-onset cases. Analysis of cardiac amyloid using surface enhanced desorption/ionization time-of-flight mass spectrometry indicated that most transthyretin (TTR) was variant in early-onset cases, while more than half was composed of wild-type TTR in late-onset cases. Although characteristics of amyloid deposits may differ among individual organs of respective cases, especially in early-onset cases, the pattern was distinct between early- and late-onset cases. Amyloid deposition in late-onset cases may be similar to that observed in senile systemic amyloidosis with wild-type TTR deposition, suggesting that aging may play an important role in these cases.

• Authors: Haruki Koike, Yukio Ando, Mitsuharu Ueda, Yuichi Kawagashira, Masahiro Iijima, Junko Fujitake, Michiyuki Hayashi, Masahiko Yamamoto, Eiichiro Mukai, Tomohiko Nakamura, Masahisa Katsuno, Naoki Hattori, Gen Sobue
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 287 Issue 1-2 Pg. 178-84 (Dec 15 2009) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 19709674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid
• Coloring Agents
• Genetic Markers
• Prealbumin
• Congo Red
• Methionine
• Valine

Topics

• Adrenal Glands (metabolism, pathology)
• Adult
• Age Factors
• Age of Onset
• Aged
• Amino Acid Sequence (genetics)
• Amino Acid Substitution (genetics)
• Amyloid (genetics, metabolism)
• Amyloid Neuropathies, Familial (genetics, pathology)
• Coloring Agents
• Congo Red
• DNA Mutational Analysis
• Female
• Genetic Markers (genetics)
• Genetic Testing
• Humans
• Kidney (metabolism, pathology)
• Male
• Methionine (genetics, metabolism)
• Middle Aged
• Myocardium (metabolism, pathology)
• Peripheral Nerves (metabolism, pathology, physiopathology)
• Prealbumin (chemistry, genetics)
• Staining and Labeling (methods)
• Valine (genetics, metabolism)
• Viscera (metabolism, pathology, physiopathology)
• Young Adult