A publication on characterization of tau pathology in the locus coeruleus in the human brain using three-dimensional imaging was recently selected as recipient of a 2023 Publication of the Year Award by the Alzheimer's Association ISTAART. The study was published in Acta Neuropathologica and involved, among others, research groups from Karolinska Institutet and Science for Life Laboratory (SciLifeLab) in Stockholm, Sweden.

The locus coeruleus (LC) in the human brain connects to virtually all parts of the central nervous system and has key roles in attention, motivations, anxiety, as well as in functions like nociception and postural muscle tone. It is involved in several neurodegenerative disorders and dysfunction gives rise to e.g. sleep disturbances, anxiety and depression in Alzheimer?s disease (AD). Pathological tau aggregation in LC has been reported for AD as well as in other tauopathies. The distribution of tau cytoskeletal pathology is associated with clinical AD progression and severity of cognitive impairment and therefore a better understanding of the origin, distribution and progression of tau pathology throughout the brain would be highly relevant.

In this study the 3D iDISCO + volume immunostaining and clearing technology was used to explore the spatiotemporal distribution of tau pathology on the cellular and regional levels in the human LC and adjacent pericoerulear (PC) structures. Some important findings were the morphological complexity and heterogeneity of AT8+ cellular structures in the LC, that gradual dendritic atrophy is the first morphological sign of the degeneration of tangle-bearing neurons, and that tau pathology is more advanced in the dorsal LC compared to the ventral LC, irrespective of the Braak NFT stage.

Link to article