2007
DOI: 10.1016/j.neuroscience.2007.01.043
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Early-onset subicular microvascular amyloid and neuroinflammation correlate with behavioral deficits in vasculotropic mutant amyloid β-protein precursor transgenic mice

Abstract: Cerebral microvascular amyloid β protein (Aβ) deposition and associated neuroinflammation are increasingly recognized as an important component leading to cognitive impairment in Alzheimer's disease and related cerebral amyloid angiopathy (CAA) disorders. Transgenic mice expressing the vasculotropic Dutch/Iowa (E693Q/D694N) mutant human Aβ precursor protein in brain (Tg-SwDI) accumulate abundant cerebral microvascular fibrillar amyloid deposits exhibiting robust neuroinflammation. In the present study, we soug… Show more

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Cited by 86 publications
(86 citation statements)
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References 34 publications
(49 reference statements)
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“…Several studies have provided evidences showing lobar CMBs as a marker of CAA. 3,24,[31][32][33] The relationship between SL CMBs and cognitive function found in the present study implies that CAA might be the underlying pathology of CMB-related cognitive impairment.…”
Section: Discussionsupporting
confidence: 49%
“…Several studies have provided evidences showing lobar CMBs as a marker of CAA. 3,24,[31][32][33] The relationship between SL CMBs and cognitive function found in the present study implies that CAA might be the underlying pathology of CMB-related cognitive impairment.…”
Section: Discussionsupporting
confidence: 49%
“…In Tg-SwDI/muAPOE mice, activated microglia are tightly associated with the development of cerebral microvascular fibrillar amyloid (Miao et al, 2005a;Fan et al, 2007;Xu et al, 2007). In these mice, the abundant parenchymal diffuse A␤ deposits do not appear to promote microglial activation.…”
Section: Discussionmentioning
confidence: 96%
“…The finding that Tg-SwDI mice accumulate extensive cerebral microvascular A␤, despite low levels of transgene-directed human A␤PP expression, appears to primarily result from ineffective clearance of Dutch/Iowa mutant A␤ from brain across the blood-brain barrier into the circulation (Davis et al, , 2006Deane et al, 2004). In Tg-SwDI mice, cerebral microvascular amyloid deposition is intimately linked with a robust neuroinflammatory response, highlighted by localized strong microglial activation and deficits in spatial learning and memory (Miao et al, 2005b;Fan et al, 2007;Xu et al, 2007).…”
Section: Introductionmentioning
confidence: 99%
“…A modified Barnes maze apparatus (Barnes, 1979) was used to assess ability to learn the location of an escape box over the course of 5 d. The Barnes maze task was chosen because we have shown recently that this test reliably detects differences in Tg-SwDI mice compared with wildtype controls and that these deficits are likely the result of specific damage to the memory-and motivation-related efferents of the hippocampus originating in the subiculum (Xu et al, 2007). The Barnes maze used is a circular table with a diameter of 91 cm, with eight 5-cm-diameter holes located equidistantly around the perimeter.…”
Section: Methodsmentioning
confidence: 99%