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.
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.
Transthyretin-related hereditary (TTR) amyloidoses represent a clinically heterogeneous group of diseases associated with various point mutations of the TTR gene.
We present a Finnish family with familial amyloidotic polyneuropathy (FAP Met30), a type of amyloidosis hitherto not described in the Finnish population.
Familial amyloidotic polyneuropathy (FAP) is a dominantly inherited form of amyloidosis usually associated with an abnormal transthyretin (TTR), previously known as prealbumin.
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.
Cellular and animal models have been developed to study the nature of APP processing and the biological and behavioral consequences of beta/A4 amyloidosis.
The gelsolin fragments isolated from at least one patient with amyloidosis have been reported to have an amino acid substitution, with asparagine replacing aspartic acid at position 187 of the plasma gelsolin.
Thus, the behavior of the transmissible brain amyloidosis parallels completely that of the transthyretinamyloidoses causing familial amyloidotic polyneuropathy, in which there are 19 different point mutations, each one of which increases enormously the likelihood of configurational change of transthyretinprealbumin to amyloid.
The amyloid forming beta-peptide of Alzheimer's disease is synthesized as part of a larger integral membrane precursor protein (beta APP) of which three alternatively spliced versions of 695, 751, and 770 amino acids have been described.