# A unified 3D reconstruction of microscopy and MRI in a brain showing Alzheimer's disease‐related neuropathology

**Authors:** Anneke Alkemade, Pierre‐Louis Bazin, Evgeniya Kirilina, Kerrin Pine, Andreas Herrler, Ronald L. A. W. Bleijs, J. Max Kros, Lysanne Groenewegen, Sanne M. M. Vermorgen, Laura E. Jonkman, Dick F. Swaab, Rawien Balesar, Nikolaus Weiskopf, Birte U. Forstmann

PMC · DOI: 10.1111/bpa.70039 · Brain Pathology · 2025-09-11

## TL;DR

This paper presents a detailed 3D reconstruction of a human brain with Alzheimer's pathology, combining MRI and microscopy data to better understand disease changes.

## Contribution

The novel contribution is a unified 3D dataset combining MRI and neuropathological data from a single Alzheimer's brain.

## Key findings

- Amyloid-β and phosphorylated-tau levels differ between left and right brain hemispheres.
- Multimodal imaging and histology data were coaligned at 200 μm resolution.
- The dataset enables detailed correlations between MRI and neuropathological observations.

## Abstract

To bridge between detailed post‐mortem neuropathological assessments and Magnetic Resonance Imaging (MRI), we have created and share a three‐dimensional (3D) account of an entire human brain with an intermediate Alzheimer's disease neuropathologic change. We combined multimodal imaging, using cryosectioning, histology, immunocytochemistry, and quantitative ultra‐high field 7 Tesla (T) magnetic resonance imaging (MRI) at submillimeter resolution. Amyloid‐β and phosphorylated‐tau immunoreactivity, cell soma, and nerve fibers were visualized, together with quantitative MR parameters. All data were coaligned with at 200 μm resolution and are openly shared. The use of whole‐brain sections allows for a detailed assessment of neuropathological alterations, revealing clear differences between the left and right hemispheres in terms of pathological load of amyloid‐β and phosphorylated‐tau in a single brain showing Alzheimer's disease neuropathologic change. This resource opens the door for a combination of detailed correlations between neuroimaging and neuropathological microscopy observations, as well as for detailed MRI validation.

Post mortem MRI was combined with neuropathological assessments at 600 μm intervals throughout the brain. Through this approach, a three dimensional account of an entire human brain with an intermediate Alzheimer's disease neuropathologic change was created. Data were reconstructed, coaligned, and combined in a downloadable resource that allows detailed correlations between neuroimaging data and microscopy observations.

## Linked entities

- **Diseases:** Alzheimer's disease (MONDO:0004975)

## Full-text entities

- **Genes:** APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}
- **Diseases:** Alzheimer's disease (MESH:D000544)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12861572/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12861572/full.md

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Source: https://tomesphere.com/paper/PMC12861572