Light PhD Seminar: The long and winding road towards dementia: an example from Alzheimer´s progression

TITLE
The long and winding road towards dementia: an example from Alzheimer's progression

ABSTRACT
At Alzheimer's disease (AD) onset, accumulation of amyloid-β (Aβ) correlates with
excitotoxicity and alteration of glutamate uptake. Experiments show that oligomeric
Aβ in mouse cultures modifies the expression of astrocytic GLT1 transporters, which
remove most of the extracellular glutamate, preventing excitotoxicity.

In this regard, we consider how extracellular Aβ modifies GLT1 expression and how
it impacts glutamate time course in the peri-synaptic space. Accordingly, we develop a
model for glutamate diffusion and uptake by astrocytic transporters in a Finite Element
Method (FEM) framework. Since extracellular glutamate and Aβ both modulate and
depend on calcium homeostasis and firing properties of the tissue, we include these
in our model to estimate the conditions for excitotoxicity. Therefore, we upscale our
description to a tissue level, and we consider the dynamics of the average firing rate,
glutamate, Aβ, and intracellular calcium concentration.

When including calcium and firing dynamics, changes in astrocytic glutamate up-
take and basal firing activity result in an intermediate state: the asymptomatic stage
of the disease that could degenerate into pathology, or reverse into a healthy brain.
These results provide theoretical support to the pivotal role of Aβ in triggering
excitotoxicity by perturbing neuronal activity, glutamate, and calcium homeostasis.
Furthermore, we can foresee the idea of Alzheimer's as a multistage disease, where transitions are driven by Aβ.

*Registration is free, but mandatory before June 23rd, 2021 To sign-up go to https://forms.gle/ixWwfaUe79zhfY388 and fill the registration form.

Link to the session: https://zoom.us/j/91757543333?pwd=ekRGYWZUeVU1WTNTK3BEK2lNT1ovZz09