A hallmark of serial age related neurodegenerative disorders, including dementia, is the intracellular accumulation of pathological tau protein in the brain.
A new study carried out by researchers in Sweden, Hungary, Canada, Germany and France is using state-of-the-art volume immune-imaging technology.
This is in combination with light sheet microscopy, in order to investigate a human brainstem nucleus called locus coeruleus, a key hub in the mammalian brain.
Locus coeruleus, a brain nucleus, is small in shape. This means that it is very difficult task to comprehensively study it with traditional 2D imaging techniques.
By use of 3D imaging of human postmortem tissue, this study reveals an interesting complexity and previously undescribed cellular forms of tau pathology in this brain region in the early stages of Alzheimer’s disease.
The study’s last author Csaba Adori says: “Our study shows that a gradual dendritic atrophy is the first morphological sign of the degeneration of tau-bearing locus coeruleus neurons, even preceding axonal lesion.
“Dendrites are crucial nerve fibres through which the neurons communicate, and dendritic degeneration leads to functional deficits like hyper-activation of neurons.
“This may contribute to several symptoms that precede the onset of Alzheimer’s disease, like sleep disturbances, anxiety and depression, which are consistent with locus coeruleus dysfunction”.
3D analysis has discovered a non-random distribution of tau-bearing locus coeruleus neurons with a clustering tendency.
The researching team also discovered that the dendrites of adjacent, clustered tau-bearing neurons often displayed dendro-dendritc contacts.
This goes in hand with the theory that pathological tau may spread via neuronal processes from one neuron to another.
Furthermore, the researching team demonstrate that tau pathology is more prominent in a part of the locus coeruleus that projects to forebrain regions that are heavily affected in Alzheimer’s disease.
The results from the study have the potential to represent a distinct advance in the understanding of how brain cell architecture may have an impact on the development and spreading of pathological tau protein.
Adori concludes: “Our results help to further understand why certain brain regions are more affected in Alzheimer’s disease than others.
“Moreover, the novel methodical approach applied to human tissue opens the way for more precise neuropathological diagnostic procedures, even in very early stages of the Alzheimer’s disease spectrum.
“This hopefully contributes to working out more effective prevention strategies in the future.”
