Familial amyloidotic polyneuropathy (FAP) is a dominantly inherited form of amyloidosis usually associated with an abnormal transthyretin (TTR), previously known as prealbumin.
Transthyretin-related hereditary (TTR) amyloidoses represent a clinically heterogeneous group of diseases associated with various point mutations of the TTR gene.
The present study demonstrates the first successful in vitro creation of amyloid-like fibrils from Asn187 gelsolin peptides and provides evidence that amyloid formation in Finnish amyloidosis is a direct consequence of the Asp187----Asn substitution in gelsolin.
Cellular and animal models have been developed to study the nature of APP processing and the biological and behavioral consequences of beta/A4 amyloidosis.
Evidence suggests that generation of such fibrils may be involved in the etiology of this disease, since mutations in the coding region of the beta/A4 amyloid precursor protein (APP) gene segregate with familial cerebral amyloidoses, including familial Alzheimer's disease.
Neuropathological findings in cerebral B-proteinamyloidosis. Differences and similarities in those cases presenting as a cerebral hemorrhage and those presenting as a dementia of the Alzheimer type.
We present a Finnish family with familial amyloidotic polyneuropathy (FAP Met30), a type of amyloidosis hitherto not described in the Finnish population.
The term "prion dementia" has been proposed to replace "spongiform encephalopathy", to accommodate the existence of atypical forms of these "prion protein" (PrP) cerebral amyloidoses that may not show spongiform changes in the brain.
The analysis of the immunohistochemical findings suggested that in the Indiana kindred the intracellular accumulation of beta PP, synaptophysin and ubiquitinated material most probably revealed a reaction of neurites to PrP-amyloid, whereas the extracellular deposition of A beta was likely an age-related phenomenon.
We conclude that in concert with other amyloid-associated serine protease inhibitors, ATIII may play a role in the pathogenesis of cerebral amyloidosis.
Our findings account for clinical heterogeneity of TTR-derived amyloidosis, and suggest the importance of substitution itself for deposits of amyloid in CTS.
Vitreous amyloidosis is a rare condition that occurs in some forms of Transthyretin hereditary Amyloidosis, mainly in Familial Amyloidotic Polyneuropathy type I. Vitreous opacities may be the earliest occurring or, in some cases, only symptom of this disorder.
Studies of the beta-amyloid precursor protein (APP), which gives rise to beta-amyloid, are rapidly leading to a better understanding of the biochemical basis of the disease--a prerequisite for rational drug development.
Ultrastructurally, amyloid-like fibrils were formed from the mutant Asn-187 and Tyr-187 gelsolin peptides corresponding to the naturally occurring missense mutations found in familial gelsolinamyloidosis syndromes, as well as from a gelsolin peptide having a Val-187 substitution.