Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice.

TitleAnti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice.
Publication TypeJournal Article
Year of Publication2005
AuthorsBrendza RP, Bacskai BJ, Cirrito JR, Simmons KA, Skoch JM, Klunk WE, Mathis CA, Bales KR, Paul SM, Hyman BT, Holtzman DM
JournalJ Clin Invest
Date Published2005 Feb
KeywordsAlzheimer Disease, Amyloid beta-Protein Precursor, Animals, Antibodies, Monoclonal, Mice, Mice, Transgenic, Neurites, Neuroaxonal Dystrophies, Plaque, Amyloid, Tomography, Optical

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.

Alternate JournalJ. Clin. Invest.
PubMed ID15668737
PubMed Central IDPMC544607
Grant ListAG020570 / AG / NIA NIH HHS / United States
AG08487 / AG / NIA NIH HHS / United States
AG13956 / AG / NIA NIH HHS / United States
AG20222 / AG / NIA NIH HHS / United States
EB00768 / EB / NIBIB NIH HHS / United States
P01 NS32636 / NS / NINDS NIH HHS / United States