Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice.
Neuritic plaques are a defining feature of Alzheimer disease (AD) pathology. These structures are composed of extracellular accumulations of amyloid-beta peptide (Abeta) and other plaque-associated proteins, surrounded by large, swollen axons and dendrites (dystrophic neurites) and activated glia. Dystrophic neurites are thought to disrupt neuronal function, but whether this damage is static, dynamic, or reversible is unknown. To address this, we monitored neuritic plaques in the brains of living PDAPP;Thy-1:YFP transgenic mice, a model that develops AD-like pathology and also stably expresses yellow fluorescent protein (YFP) in a subset of neurons in the brain. Using multiphoton microscopy, we observed and monitored amyloid through cranial windows in PDAPP;Thy-1:YFP double-transgenic mice using the in vivo amyloid-imaging fluorophore methoxy-X04, and individual YFP-labeled dystrophic neurites by their inherent fluorescence. In vivo studies using this system suggest that amyloid-associated dystrophic neurites are relatively stable structures in PDAPP;Thy-1:YFP transgenic mice over several days. However, a significant reduction in the number and size of dystrophic neurites was seen 3 days after Abeta deposits were cleared by anti-Abeta antibody treatment. This analysis suggests that ongoing axonal and dendritic damage is secondary to Abeta and is, in part, rapidly reversible.
Brendza
Robert P
RP
Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Bacskai
Brian J
BJ
Cirrito
John R
JR
Simmons
Kelly A
KA
Skoch
Jesse M
JM
Klunk
William E
WE
Mathis
Chester A
CA
Bales
Kelly R
KR
Paul
Steven M
SM
Hyman
Bradley T
BT
Holtzman
David M
DM
D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D019150:Neuroaxonal Dystrophies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011859:Radiography; D041622:Tomography, Optical
D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal