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In particular, despite the A\u03b2 neurotoxicity indicated by<jats:italic>in vitro<\/jats:italic>studies, mouse models with significant A\u03b2 deposition lack robust and progressive loss of forebrain neurons. Such results have fueled the view that A\u03b2 pathology is insufficient for neurodegeneration<jats:italic>in vivo<\/jats:italic>. In this study, because monoaminergic (MAergic) neurons show degenerative changes at early stages of AD, we examined whether the<jats:italic>APPswe\/PS1<\/jats:italic>\u0394<jats:italic>E9<\/jats:italic>mouse model recapitulates progressive MAergic neurodegeneration occurring in AD cases. We show that the progression forebrain A\u03b2 deposition in the<jats:italic>APPswe\/PS1<\/jats:italic>\u0394<jats:italic>E9<\/jats:italic>model is associated with progressive losses of the forebrain MAergic afferents. Significantly, axonal degeneration is associated with significant atrophy of cell bodies and eventually leads to robust loss (\u223c50%) of subcortical MAergic neurons. Degeneration of these neurons occurs without obvious local A\u03b2 or tau pathology at the subcortical sites and precedes the onset of anxiety-associated behavior in the mice. Our results show that a transgenic mouse model of A\u03b2 pathology develops progressive MAergic neurodegeneration occurring in AD cases.<\/jats:p>","DOI":"10.1523\/jneurosci.4218-08.2008","type":"journal-article","created":{"date-parts":[[2008,12,17]],"date-time":"2008-12-17T17:23:20Z","timestamp":1229534600000},"page":"13805-13814","source":"Crossref","is-referenced-by-count":182,"title":["Amyloid Pathology Is Associated with Progressive Monoaminergic Neurodegeneration in a Transgenic Mouse Model of Alzheimer's Disease"],"prefix":"10.1523","volume":"28","author":[{"given":"Ying","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Jeong","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Savonenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda","family":"Stirling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Borchelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mamounas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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