3D imaging contributes to a better understanding of the early stages of Alzheimer’s disease

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– Our study shows that progressive shrinkage (atrophy) of dendrite projections is the first morphological sign of degeneration of tau-bearing afferent neurons, and thus also before axonal damage. Dendrites are the structure that receives impulses from other neurons and is therefore essential for communication in the brain. Degeneration of dendrites can lead to serious functional disorders such as hyperactivity of neurons. This may contribute to many of the pre-ADZ symptoms, including sleep disturbances, anxiety and depression, all of which may be related to disturbed function in the blue locus, says the study’s final author. Chapa Adoriresearcher in Department of NeuroscienceKarolinska Institutet.

Supports previous discoveries in the lab

3D analysis revealed a nonrandom distribution of tau-bearing rosacea neurons with the direction of aggregation. The researchers also discovered that dendrites in adjacent tau-bearing clumps of neurons often exhibit dendritic connections. This is in line with the theory that pathological tau can spread through neuronal protrusions from one neuron to another, previous in vitro and animal studies suggest.

In addition, the researchers showed that tau pathology is more prominent in the part of the blue locus that directs to the areas of the forebrain most affected by Alzheimer’s disease.

The findings may represent a clear advance in understanding how brain cell structure influences the development and spread of pathological tau.

Our findings contribute to an increased understanding of why certain areas of the brain are more affected by Alzheimer’s disease than others. In addition, the new methodology applied to human tissue opens the way for more accurate neurodiagnostic procedures, even in the very early stages of the Alzheimer’s disease spectrum. It is hoped that this will contribute to the development of more effective preventive strategies to prevent Alzheimer’s disease in the future, says Chapa Adori.

The study was supported by the Brain Foundation, Olle Engkvist Foundation, Åhlen Foundation, Dementia Society, Lars Hiertas Memory Foundation, Karolinska Institute, Knut and Alice Wallenberg Foundation, Swedish Research Council, Rossy Family Foundation, Edmund J. Safra Charitable Foundation, and the Hungarian National Brain Research Programme.

On the Csaba Adori . website More information is available and 3D presentations in English.

Publishing

“Spatiotemporal characterization of cellular tau pathology in the human blue-bubbly complex site by 3D imaging.Abris Gilvesi, Evelina Hossen, Zofia Maglowski, Ursulia Mihaly, Tibor Hortobagy, Shijiaki Kanatani, Helmut Hensen, Nicholas Rene, Thomas Hockfelt, Jan Mulder, Mathias Olin, Gabor J. Kovacs, and Kassaba Adori. Acta Neuropathologiconline August 30, 2022, doi: 10.1007/s00401-022-02477-6.