[The CNS amyloid].
BACKGROUND
In this article we wish to review the most relevant pathogenic aspects and histological characteristics of the deposition of amyloid in the central nervous system (CNS).


METHODS
The beta A4, a product of protein APP, codified on chromosome 21, is related to sporadic cerebral amyloid angiopathy not associated with dementia, Alzheimer's disease, senile dementia of Alzheimer type or Down's syndrome, whilst a specific mutation on the 693 codon of the gene which codifies beta-APP is related to hereditary haemorrhage with Dutch-type amyloid angiopathy. The gene which codifies cystatin C, a member of the family of cystatin genes grouped on chromosome 20p11.2, undergoes specific mutation giving rise to a mutant protein which, at the position 68, substitutes leucine for glutamine. The mutant cystatin C has a greater tendency to aggregation when the temperature is increased. This pathogenic molecular mechanism underlies cases of amyloidosis due to hereditary type cystatin C, considered to be a systemic amylosidosis. The formation and deposition of amyloid may also occur in other neurodegenerative diseases of animals and humans in relation to the accumulation of abnormal isoforms of the prion protein, especially in Gerstman-Straussler-Scheinke's disease and the Japanese type of prion cerebral amyloid angiopathy. The fact that these aberrant isoforms mostly undergo conformational changes involving a shift from alpha-helix to beta-sheet structure is basic to the amyloidogenesis of prion disease.


CONCLUSIONS
Amyloid is a family of proteins which is physically, chemically and structurally related, with common histochemical characteristics. In the CNS it is deposited in the vessel walls and parenchyma with topographic patterns and morphological differences according to the different disorders in which the amyloid is involved. Only neuropathological studies will enable us to discover its true incidence in senility with or without clinical features of dementia, and with or without haemorrhagic changes.
Departamento de Anatomía Patológica/Neuropatología, Universidad Autónoma, Hospital de la Vall d'Hebron, Barcelona, España. fjromero@omc.telprof.es
A
A
Ortega-Aznar
J
J
de la Torre
J
J
Castellví
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000378:metabolism*; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D015891:Cystatins / Q000235:genetics; D006801:Humans; D017354:Point Mutation / Q000235:genetics
D000682:Amyloid; D016229:Amyloid beta-Peptides; D015891:Cystatins