Dataset Information

Astrocytosis precedes amyloid plaque deposition in Alzheimer APPswe transgenic mouse brain: a correlative positron emission tomography and in vitro imaging study.

ABSTRACT:

Purpose

Pathological studies suggest that neuroinflammation is exacerbated by increased beta-amyloid (A?) levels in the brain early in Alzheimer's disease (AD). The time course and relationships between astrocytosis and A? deposition were examined using multitracer in vivo positron emission tomography (PET) imaging in an AD transgenic mouse model, followed by postmortem autoradiography and immunohistochemistry analysis.

Methods

PET imaging with the amyloid plaque tracer (11)C-AZD2184 and the astroglial tracer (11)C-deuterium-L-deprenyl ((11)C-DED) was carried out in APPswe mice aged 6, 8-15 and 18-24 months (4-6 animals/group) and in wild-type (wt) mice aged 8-15 and 18-24 months (3-6 animals/group). Tracer uptake was quantified by region of interest analysis using PMOD software and a 3-D digital mouse brain atlas. Postmortem brain tissues from the same APPswe and wt mice in all age groups were analysed for A? deposition and astrocytosis by in vitro autoradiography using (3)H-AZD2184, (3)H-Pittsburgh compound B (PIB) and (3)H-L-deprenyl and immunostaining performed with antibodies for A?42 and glial fibrillary acidic protein (GFAP) in sagittal brain sections.

Results

(11)C-AZD2184 PET retention in the cerebral cortices of APPswe mice was significantly higher at 18-24 months than in age-matched wt mice. Cortical and hippocampal (11)C-DED PET binding was significantly higher at 6 months than at 8-15 months or 18-24 months in APPswe mice, and it was also higher than at 8-15 months in wt mice. In vitro autoradiography (3)H-AZD2184 and (3)H-PIB binding confirmed the in vivo findings with (11)C-AZD2184 and demonstrated age-dependent increases in A? deposition in APPswe cortex and hippocampus. There were no significant differences between APPswe and wt mice in (3)H-L-deprenyl autoradiography binding across age groups. Immunohistochemical quantification demonstrated more A?42 deposits in the cortex and hippocampus and more GFAP(+) reactive astrocytes in the hippocampus at 18-24 months than at 6 months in APPswe mice.

Conclusion

The findings provide further in vivo evidence that astrocytosis occurs early in AD, preceding A? plaque deposition.

SUBMITTER: Rodriguez-Vieitez E

PROVIDER: S-EPMC4424277 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Publications

Astrocytosis precedes amyloid plaque deposition in Alzheimer APPswe transgenic mouse brain: a correlative positron emission tomography and in vitro imaging study.

Rodriguez-Vieitez Elena E Ni Ruiqing R Gulyás Balázs B Tóth Miklós M Häggkvist Jenny J Halldin Christer C Voytenko Larysa L Marutle Amelia A Nordberg Agneta A

European journal of nuclear medicine and molecular imaging 20150417 7

<h4>Purpose</h4>Pathological studies suggest that neuroinflammation is exacerbated by increased beta-amyloid (Aβ) levels in the brain early in Alzheimer's disease (AD). The time course and relationships between astrocytosis and Aβ deposition were examined using multitracer in vivo positron emission tomography (PET) imaging in an AD transgenic mouse model, followed by postmortem autoradiography and immunohistochemistry analysis.<h4>Methods</h4>PET imaging with the amyloid plaque tracer (11)C-AZD2 ...[more]

PMID: 25893384

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Dataset Information

Astrocytosis precedes amyloid plaque deposition in Alzheimer APPswe transgenic mouse brain: a correlative positron emission tomography and in vitro imaging study.

Purpose

Methods

Results

Conclusion

Publications

Astrocytosis precedes amyloid plaque deposition in Alzheimer APPswe transgenic mouse brain: a correlative positron emission tomography and in vitro imaging study.

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