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Updated: Jan 29, 2026

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons
Published on: October 30, 2018
Amyloid β perturbs elevated heme flux induced with neuronal development
Chantal Vidal1, Kelly Daescu1, Keely E Fitzgerald1
1Department of Biological Sciences, University of Texas at Dallas, Richardson, TX, USA.
Introduction:
Heme is a central molecule in mitochondrial respiration and ATP generation in neuronal cells. Thus, we assessed the importance of altered heme metabolism in Alzheimer's disease (AD) pathogenesis.
Methods:
To investigate the role of altered heme metabolism in AD, we identified heme-related proteins whose expression is altered in AD patients and mouse models exhibiting amyloid pathology. We detected the levels of proteins involved in heme synthesis, uptake, degradation, and function during neuronal differentiation and characterized the effects of Aβ.
Results:
We found that the expression levels of the rate-limiting heme synthetic enzyme ALAS1 and heme degradation enzyme HO-2 are selectively decreased in AD patients and mice. Aβ selectively reduces the levels of HO-2 and heme degradation, which are elevated to support neuronal functions in fully differentiated neuronal cells.
Discussion:
Our data show that lowered heme metabolism, particularly the decreased levels of heme degradation and HO-2, is likely a very early event in AD pathogenesis.
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