In vivo reversal of amyloid-beta lesions in rat brain.
Cerebral amyloid-beta (Abeta) deposition is central to the neuropathological definition of Alzheimer disease (AD) with Abeta related toxicity being linked to its beta-sheet conformation and/or aggregation. We show that a beta-sheet breaker peptide (iAbeta5) dose-dependently and reproducibly induced in vivo disassembly of fibrillar amyloid deposits, with control peptides having no effect. The iAbeta5-induced disassembly prevented and/or reversed neuronal shrinkage caused by Abeta and reduced the extent of interleukin-1beta positive microglia-like cells that surround the Abeta deposits. These findings suggest that beta-sheet breakers, such as iAbeta5 or similar peptidomimetic compounds, may be useful for reducing the size and/or number of cerebral amyloid plaques in AD, and subsequently diminishing Abeta-related histopathology.
Sigurdsson
E M
EM
Department of Pathology, New York University Medical Center, New York 10016, USA.
Permanne
B
B
Soto
C
C
Wisniewski
T
T
Frangione
B
B
D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D000679:Amygdala / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D008297:Male; D017628:Microglia / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)