Transthyretin amyloidosis: A new mutation associated with dementia

R. B. Petersen, H. Goren, M. Cohen, S. L. Richardson, N. Tresser, A. Lynn, M. Gali, M. Estes, P. Gambetti

Research output: Contribution to journalArticlepeer-review

119 Scopus citations


Familial transthyretin (TTR) amyloidosis commonly presents with peripheral neuropathy and involvement of visceral organs. In contrast, signs of central nervous system (CNS) involvement are exceptional. We report that members of a kindred affected by a slowly progressive dementia, seizures, ataxia, hemiparesis, and decreased vision without neuropathy have TTR amyloid deposits in the leptomeninges, the brain parenchyma, and the eye. This condition, previously labeled oculoleptomeningeal amyloidosis, is linked to a mutation at codon 30 of TTR gene, resulting in the substitution of valine with glycine in this family, TTR amyloid deposits were present in the leptomeninges, especially the leptomeningeal vessels, and in the subependymal regions of the ventricular system where they disrupted the ependymal lining and resulted in amyloid-glial formations protruding into and narrowing the ventricular system. Hydrocephalus and atrophy and infarction of cerebral and cerebellar cortexes were also present. Review of the literature shows that amyloid deposition in the leptomeninges is not uncommon in TTR amyloidoses clinically characterized by peripheral neuropathy and lack of CNS signs. The present kindred, which presented exclusively with signs of CNS involvement, expands the phenotype of TTR amyloidosis and raises questions concerning the mechanisms determining phenotypic expression in TTR familial amyloidosis.

Original languageEnglish
Pages (from-to)307-313
Number of pages7
JournalAnnals of Neurology
Issue number3
StatePublished - 1997


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