# Multiplex digital spatial profiling identifies subregion dependent targeted proteome changes across variants of dementia

## TL;DR

This study uses spatial profiling to identify how protein changes vary in different brain regions and dementia types, helping to better understand and diagnose dementia.

## Contribution

The study introduces a method to spatially map proteome changes in specific brain layers across different dementia variants.

## Key findings

- Layers II-V of the cortex showed the most protein dysregulation in dementia patients compared to healthy controls.
- Phosphorylated tau and Aβ42 were spatially enriched in specific cortical sublayers, not uniformly distributed.
- Region-specific protein localization could serve as unique biomarkers for different dementia types.

## Abstract

Frontotemporal lobar degeneration (FTLD) is the leading cause of dementia in patients under the age of 65. Even in a single anatomical region, there is variance within pathological protein deposition within the FTLD spectrum, which drives difficulty in post-mortem clinicopathological diagnoses. We spatially multiplexed the proteome geography at two levels of the cortex and the subcortical white matter in patients with various types of dementia (Alzheimer’s disease, C9orf72, MAPT also referred to as FTLD-tau, FTLD-TDP, FTLD-GRN; n = 6 per syndrome) and neurologically healthy controls (NHC). Layers II-V of the cortex from diseased individuals displayed the greatest protein dysregulation as compared to NHC. Traditional biomarkers of dementia, like phosphorylated tau proteins and Aβ42 displayed dysregulation, however, our data suggest spatial enrichment distinct to cortical sublayers. In conclusion, the specific localization of these protein deposits could be used to elucidate region-specific pathologic biomarkers unique to individual variants of dementia.