Premium
O1‐03‐05: Neuroimaging in living APP transgenic mice reveals unexpected findings
Author(s) -
Luo Feng,
Zhang Yumin,
Mudd Sarah,
Cole Todd,
Seifert Terese,
Cox Bryan,
Fox Gerard
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.209
Subject(s) - neuroimaging , medicine , voxel , disease , clinical trial , nuclear medicine , pathology , neuroscience , psychology , radiology , psychiatry
examined. Results: Abeta1-42 or KLH vaccinations were started when disease progression and cognitive deficits are observed (12mos), and continued for an additional 4 months. Vaccinated APPSwDI/NOS2-/mice, which have predominantly vascular amyloid pathology, showed decreased brain Abeta (30%) and reduced tau (AT8 positive) hyperphosphorylation (30-40%). Neuron loss and cognitive deficits were partially reduced compared to mice receiving control vaccination. In APPSw/NOS2-/vaccinated mice, brain Ab was reduced by 65-85 percent and hyperphosphorylated tau by 50-60%. Lowering amyloid prevented further neuron loss and completely reversed memory deficits in these mice. Importantly, microhemorrhage was observed in all vaccinated APPSw/NOS2-/mice. Conclusions: These data support the amyloid cascade hypothesis of AD, but also suggest that NO plays a protective role in reducing downstream pathology. While bolstering the confidence in amyloid as a therapeutic target for AD, the resulting brain microhemorrhage cannot be ignored. Interventions that lower amyloid without microhemorrhage may be important new therapeutic approaches for AD.