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. 2010 Nov 12;330(6006):980-2.
doi: 10.1126/science.1194516. Epub 2010 Oct 21.

Peripherally Applied Abeta-containing Inoculates Induce Cerebral Beta-Amyloidosis

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Peripherally Applied Abeta-containing Inoculates Induce Cerebral Beta-Amyloidosis

Yvonne S Eisele et al. Science. .
Free PMC article


The intracerebral injection of β-amyloid-containing brain extracts can induce cerebral β-amyloidosis and associated pathologies in susceptible hosts. We found that intraperitoneal inoculation with β-amyloid-rich extracts induced β-amyloidosis in the brains of β-amyloid precursor protein transgenic mice after prolonged incubation times.


Fig. 1
Fig. 1. Induced Aβ deposition
(A, B) Aβ-immunostained frontal cortex of APP23 mice inoculated intraperitoneally with Tg extract (A) or Wt extract- (B). (C, D) Most induced β-amyloid was vascular (Aβ-CAA), with Aβ-immunoreactivity extending into the brain parenchyma (arrows). Amyloid-laden vessels were congophilic [red in (D); birefringent under cross-polarized light in insert] and often were surrounded by diffuse, Congo red-negative Aβ deposits (arrowheads). (E, F) Analysis of the entire neocortex for Aβ-CAA frequency [indicated are all three (I-III) CAA severity grades (5)], and for total Aβ load in Tg extract-inoculated mice compared with control (Ctr) mice. Cohort 1 consisted of six Tg extract-inoculated mice versus seven untreated control mice. Aβ-CAA: t(11)=6.78 (all severity grades combined), ***p<0.0001; Aβ load: t(11)=8.79, ***p<0.0001. Cohort 2 consisted of five Tg extract-inoculated mice versus five Wt extract-inoculated mice and four PBS-injected mice. These latter two (control) groups did not differ significantly and were combined for analysis. Aβ-CAA: t(12)=7.79, ***p<0.0001; Aβ load t(12)=2.71, *p<0.05. The occasional parenchymal Aβ-deposits in control mice are normal for 9-month-old APP23 mice. Error bars, means ±SEM. Scale bars: [(A) and (B)] 200μm; [0(C) and (D)] 50μm.
Fig. 2
Fig. 2. Induced Aβ deposition was linked to multiple associated pathologies
(A) Ultrastructural analysis showed amyloid deposition within the vascular basal lamina (BL), with typical amyloid fibrils (arrowheads) extending into the brain parenchyma. Insets are low- and high-magnification views of the examined vessel (L, lumen) and the typical nonbranching amyloid fibrils. (B to E) Vascular amyloid [stained by Congo Red in (B) and (C)] and parenchymal plaques were surrounded by hypertrophic, Iba1-positive microglia (B), Glial fibrillary acidic protein (GFAP)-positive astrocytes (C), hyperphosphorylated tau-positive neurites [(D); asterisk indicates amyloid core], but a paucity of proximate neurons [cresyl-violet stain (E)]. (F and G) Vessels with CAA types II and III showed smooth muscle cell loss at the site of amyloid deposition (arrowheads; confocal image, maximum projection of 5μm z-stack: red, Aβ; green, smooth muscle actin). A normal vessel (G) has a complete ring of smooth muscle cells. (H) Immunoblotting of micropunches of Aβ-immunoreactive material revealed the expected Aβ band. Synthetic Aβ40/42 is shown as control. Markers, 3 and 6 kD. Scale bars: (A) 1μm (insets, 5 and 0.5 μm); [(B) to (E)] 50μm; [(F) and (G)] 10μm.

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