Amyloid neuropathology in the single Arctic APP transgenic model affects interconnected brain regions
2012 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, no 4, 831.e11Article in journal (Refereed) Published
The Arctic APP mutation (E693G) within the amyloid beta (A beta) domain of amyloid precursor protein (APP) leads to dementia with clinical features similar to Alzheimer's disease (AD), which is believed to be mediated via increased formation of protofibrils. We have generated a transgenic mouse model, TgAPParc, with neuron-specific expression of human amyloid precursor protein with the Arctic mutation (hAPParc), showing mild amyloid pathology with a relatively late onset. Here we performed a detailed analysis of the spatiotemporal progression of neuropathology in homozygous TgAPParc, focusing on intracellular A beta and diffuse A beta aggregates rather than amyloid plaques. We show that the neuropathology in homozygous TgAPParc mice starts with intracellular A beta aggregates, which is followed by diffuse extracellular A beta deposits in subiculum that later expands to brain regions receiving neuronal projections from regions already affected. Together this suggests that the pathology in TgAPParc mice affects interconnected brain regions and may represent a valuable tool to study the spread and progression of neuropathology in Alzheimer's disease.
Place, publisher, year, edition, pages
2012. Vol. 33, no 4, 831.e11
Alzheimer's disease, Transgenic animal model, Amyloid beta, Arctic mutation, Intracellular abeta
IdentifiersURN: urn:nbn:se:uu:diva-259749DOI: 10.1016/j.neurobiolaging.2011.07.012ISI: 000301506800037PubMedID: 21880397OAI: oai:DiVA.org:uu-259749DiVA: diva2:845283