Beta-protein deposition: a pathogenetic link between Alzheimer's disease and cerebral amyloid angiopathies.
Cerebral amyloid angiopathy (CAA) refers to a group of hereditary (hereditary cerebral hemorrhage with amyloidosis, HCHWA and sporadic (SCAA) disorders characterized by amyloid fibril deposition restricted to the leptomeningeal and cortical vasculature leading to recurrent hemorrhagic and/or ischemic accidents. On clinical and biochemical grounds, two forms of HCHWA can be distinguished. The amyloid subunit of the HCHWA of Icelandic origin is related to Cystatin C, while amyloid from patients of Dutch origin (HCHWA-D) is related to the beta-protein (or A4), the main component of vascular and plaque core amyloid in Alzheimer's disease (AD) and Down's syndrome (DS) [corrected]. SCAA is an increasingly recognized cause of stroke in normotensive individual amounting to 5-10% of all cerebrovascular accidents. We now report the isolation and partial amino acid sequence of the amyloid subunit from a case of SCAA and a new case of HCHWA-D. The recognition that a heterogeneous group of diseases are linked by similar pathological and chemical features suggests that diversity of etiological factors may promote a common pathogenetic mechanism leading to amyloid-beta (A beta) deposition, and open new ways of research in AD and CAA as they are related to dementia and stroke.
Coria
F
F
Department of Pathology, New York University Medical Center, NY 10016.
Prelli
F
F
Castaño
E M
EM
Larrondo-Lillo
M
M
Fernandez-Gonzalez
J
J
van Duinen
S G
SG
Bots
G T
GT
Luyendijk
W
W
Shelanski
M L
ML
Frangione
B
B
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000682:Amyloid / Q000302:isolation & purification* / Q000378:metabolism; D016229:Amyloid beta-Peptides; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000378:metabolism* / Q000473:pathology; D006801:Humans
D000682:Amyloid; D016229:Amyloid beta-Peptides