Mouse Mesoscale Connectivity in Aging and Alzheimer’s Disease
Axonal projections were labeled with stereotaxic injections of viral tracers in mouse models of Alzheimer’s disease and their aged littermates. Whole brain axonal trajectories were quantified using the standardized platform for the Allen Mouse Brain Connectivity Atlas to generate a database of neural projections in aging and diseased mice. Amyloid beta plaques were also labeled in mice with amyloid pathology, and brain-wide plaque density was quantified using an automated pipeline. This dataset can be compared with the projections of young adult (p56) mice in the Allen Mouse Brain Connectivity Atlas to identify differences in anatomy and connectivity that occur in aging and Alzheimer’s disease.
The data can be downloaded using URLs in this manifest file (330K images listed):
OVerview of the data
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Whole brain images and automated detection of axonal projections from stereotaxic injections of fluorescent viral tracers.
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Whole brain images and automated detection of plaques labeled with methoxy-X04 injections
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Axonal projections quantified over structures (unionizes)
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Detected axonal projections and plaques registered to CCFv3 and gridded at 10, 25, and 100 um resolution.
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Automatically detected dystrophic neurites registered to CCFv3 and gridded at 10, 25, and 100 um resolution.
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Deformation values from registration
Related Mouse Lines
These data were generated from stereotaxic injections into the following Alzheimer’s disease and frontotemporal dementia mouse lines.
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Mouse Line |
Description |
Source |
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APP/PS1 |
Express chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) with the Swedish mutations (K595N/M596L) and a mutant human presenilin 1 (PS1-dE9). Expression is driven by the mouse prion protein promotor (moPrP) |
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hAPP-J20 |
Express a mutant form of the human amyloid protein precursor bearing both the Swedish (K670N/M671L) and the Indiana (V717F) mutations (APPSwInd). Expression is driven by the human platelet-derived growth factor beta polypeptide (PDGFb) promoter. |
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rTg4510 |
These bitransgenic mice express tauP301L in forebrain. The tetO-MAPT*P301L transgene has the Tet-responsive element (TRE or tetO) and mouse prion protein promoter sequences (PrP or Prnp) directing expression of the P301L mutant variant of human four-repeat microtubule-associated protein tau (4R0N tauP301L). It is crossed with CaMK2a-tTA mice so that expression of tauP301L is driven by the CaMK2a promotor in the absence of doxycycline. |
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Tg2576 |
Overexpression of the human APP gene encoding the APP695.SWE mutation (K670N and M671L). The construct contained the APP gene fused to the hamster prion protein promoter (haPrP). |
Experiments
There are five experiments in this dataset:
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Brain-wide mapping 12-15 mo APP/PS1 mice and their littermate controls.
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Projection mapping in Cre driver lines crossed to the APP/PS1 mouse line, used to target specific cell classes (12-18 mo).
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Targeted mapping of specific regions in various mouse lines and ages.
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Selective mapping focused on ENTm in APP/PS1 mice crossed to the rTg4510 tauopathy line.
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Target-defined mapping using intersectional viral tracing in APP/PS1 and hAPP-J20 mouse lines.
Acknowledgment
This project was supported by the National Institute on Aging and the National Institutes of Health by Award Number R01AG047589. Its contents are solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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