Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro.
Numerous studies have established a linkage between the apolipoprotein (apo) E4 allele and late-onset Alzheimer's disease. It remains unclear if apo E plays a direct role in the pathogenesis of Alzheimer's disease and what, if any, are its significant interactions with amyloid beta (A beta) and tau. Apo E has been found immunohistochemically in all types of amyloid deposits and apo E fragments have been isolated from amyloid. Furthermore, apo E has been shown to bind soluble A beta. It has been proposed that apo E acts to promote and/or modulate A beta fibril formation. It is well established that peptides homologous to A beta will form amyloid-like fibrils in solution. With the use of electron microscopy and a thioflavin T assay for fibril formation we found that apo E and apo E4 in particular enhance this spontaneous fibrillogenesis of A beta peptides under the in vitro conditions used. These in vitro data suggest that the apo E4 isoform is a risk factor for Alzheimer's disease that acts to accelerate a process that can occur in its absence.
Wisniewski
T
T
Department of Pathology, New York University Medical Center, NY 10016.
Castaño
E M
EM
Golabek
A
A
Vogel
T
T
Frangione
B
B
D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010455:Peptides
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010455:Peptides