Neurons can last a lifetime, so how do these cells cope with repetitive stress exposure?
In a previous study published in EJN (Doehner, 2012), Knuesel’s Lab investigated the ultrastructural properties of Reelin-positive granular aggregates (typical feature of aging) and found accumulation of Reelin in varicosities in dendritic and axonal compartments, particularly in aged immune-challenged mice. The authors interpreted these neuronal extrusions to be a mechanism of neuronal defense against protein deposits, allowing their clearance by glia. They also hypothesized that chronic neuroinflammation could lead to the failure of neurons to extrude these aggregates and to pathological aging. In line with this hypothesis, Knuesel’s lab more recently showed a double-immune challenge led to AD-like plaques in wild-type aging mice (Krstic, 2012).
Part 1: In the first part of this EJN interview, Irene Knuesel’s close collaborator, Dimitrije Krstic presents how the phenotypical features of their aging immune-challenged mice model are reminiscent of the post-mortem findings in human patients with AD.
Part 2: In the second part of this interview, Irene Knuesel explains how this study in combination with findings published by other research groups, have led them to a new hypothesis on the sequence of cellular events leading to Alzheimer’s Disease (Krstic, 2013).
Part 3: Following these two presentations, the speakers reply to the following questions:
Q1: Are anti-inflammatory drugs protective against AD?
Q2: Is there an association between infection-induced neuroinflammation and AD?
Q3: How do the known genetic risk factors of AD fit with Knuesel’s AD hypothesis?
Q4: What about other risk factors of AD?
Q5: Could axonopathy also play a causal role in familial AD?
Q6: Are the cellular events described in Knuesel’s model relevant to other neurodegenerative disease?
Part 4: Concluding remarks and perspectives
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