Plaque morphology and composition analysis with Amytracker and MALDI-MSI

A study by Minta et al. 2026 published in Acta Neuropathologica Communications used MALDI-MSI to identify differences between the specific assembly of Aβ plaques in AD and DS that would have been missed by conventional bulk-measurement approaches. In their study, Amytracker staining was used both as a means to evaluate Aβ plaque and NFT morphology in tissue samples, as well as to corroborate their cluster-based MALDI-MSI plaque identification method.

Plaque morphology differs in Alzheimer’s disease (AD) and Down syndrome (DS)

Alzheimer’s disease (AD) and Down syndrome (DS) are characterised by amyloid-β (Aβ) pathology in the brain, but the mechanisms leading to plaque formation differ. To understand the molecular heterogeneity of individual plaques the authors employ a combination of stainging plaques using Amytracker and matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI). This allowed to analyze the composition as well as the spatial context of aggregates in AD, SD and healthy brain tissue. Using Amytracker 520 the overall abundance of Aβ plaques and neurofibrillary tangles (NFTs) was similar between AD and DS tissues but Amytracker staining revealed that DS displayed fewer, but much larger aggregates while AD pathology was more dispersed. When individual plaque composition was compared using MALDI-MSI, the authors found that Aβ truncation patterns differ significantly between AD and DS plaques, hinting at different mechanisms of Aβ processing. They also identified unique co-localisation patterns between different Aβ species in AD that were not present in DS. While MALDI-MSI could independently identify plaques based on cluster identification of Aβ peptides, Amytracker staining was used to confirm correct plaque assignment.

Image:Amytracker 520 stains Aβ plaques and NFTs in AD and DS tissue samples. Top: Amytracker reveals morphological differences in Aβ plaque and NFT size and abundance between AD (A), DS (B) and healthy control (C) brain tissue. Bottom: Amytracker staining (C) confirms cluster-based MALDI-MSI Aβ plaque identification (D), as shown by overlapping the two images in (E). Adaped from Figure 3 in Minta et al. 2026, (CC BY).

Read More:

• Karolina Minta, Linda Söderberg, Eleni Gkanatsiou, Malin Johannesson, Christer Möller, My Björklund, Gunilla Osswald, Lars Lannfelt, Susanne Fabre & Wojciech Michno. MALDI mass spectrometry imaging (MSI) reveals molecular and structural heterogeneity of amyloid-β in sporadic Alzheimer’s disease and Down syndrome. Acta Neuropathol Commun 14, 87 (2026).