Does Alzheimer's disease start inside nerve cells?

Date:
August 18, 2021
Source:
Lund University
Summary:
An experimental study has revealed that the Alzheimer's protein
amyloid- beta accumulates inside nerve cells, and that the
misfolded protein may then spread from cell to cell via nerve
fibers. This happens at an earlier stage than the formation of
amyloid-beta plaques in the brain, something that is associated
with the progression of Alzheimer's disease.



FULL STORY ==========================================================================
An experimental study from Lund University in Sweden has revealed that
the Alzheimer's protein amyloid-beta accumulates inside nerve cells,
and that the misfolded protein may then spread from cell to cell via
nerve fibres. This happens at an earlier stage than the formation of amyloid-beta plaques in the brain, something that is associated with
the progression of Alzheimer's disease.


==========================================================================
The study in question builds on previous research based on amyloid-beta's prion-like properties. This means that the protein adopts a misfolded form
that acts as a template for spreading in the brain, where it accumulates
and develops plaques. "The plaques of amyloid-beta outside the nerve
cells have long been a target for treatment of Alzheimer's disease. But
as treatments to remove plaque have not helped against dementia, we must develop and investigate other hypotheses in order to find other targets
for treatment. Our results indicate that amyloid-beta is highly relevant,
but that we must focus on misfolded amyloid-beta inside the nerve cells
that arise far earlier than the visible plaques," says the first author
of the study Tomas Roos, doctoral student at Lund University and resident physician at Skaane University Hospital's neurological clinic.

Amyloid-beta is present in the brain of healthy individuals, but the
mechanisms that are disrupted and cause the misfolding remain unclear. The plaques are extracellular, but the results of this study indicate that a misfolding can occur within the cells. Furthermore, the researchers show
that there is a continuous exchange of amyloid-beta between the outside
and inside of nerve cells, a kind of equilibrium, that is disturbed when misfolded amyloid-beta accumulates both inside and outside nerve cells.

In the study, which was conducted using a mouse model for Alzheimer's
and cell culture, the researchers also noted that misfolded amyloid-beta
inside the nerve cells leads to increased amyloid-beta production.

"The increased amyloid-beta caused by misfolded amyloid-beta inside
cells can bring about a vicious circle of more and more amyloid-beta production. This could explain the enormous amounts of amyloid-beta that accumulate in the brain of Alzheimer's patients. First and foremost,
the study results are to be replicated in a different Alzheimer's
model. However, our results indicate that many of amyloid-beta's damaging effects may be caused by what is happening within the cells, independent
of plaques. This may explain why so many experimental treatments targeting plaques outside the nerve cells have failed and that we should focus
our attention inwards," concludes Tomas Roos.

========================================================================== Story Source: Materials provided by Lund_University. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Tomas T. Roos, Megg G. Garcia, Isak Martinsson, Rana Mabrouk, Bodil
Israelsson, Tomas Deierborg, Asgeir Kobro-Flatmoen, Heikki Tanila,
Gunnar K. Gouras. Neuronal spreading and plaque induction of
intracellular Ab and its disruption of Ab homeostasis. Acta
Neuropathologica, 2021; DOI: 10.1007/s00401-021-02345-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210818130550.htm

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