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Zetterberg H, Mörtberg E, Song L, Chang L, Provuncher GK, Patel PP, Ferrell E, Fournier DR, Kan CW, Campbell TG, Meyer R, Rivnak AJ, Pink BA, Minnehan KA, Piech T, Rissin DM, Duffy DC, Rubertsson S, Wilson DH, Blennow K. Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid β levels in humans. PLoS One. 2011;6(12):e28263. PubMed.
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University of California, Irvine
This is a fantastic study with important implications. It illustrates the link between oxygen levels and the production of Aβ—something on which I conducted my Ph.D. over 10 years ago. It also suggests that this effect is probably body-wide, rather than restricted to the brain, since large increases of Aβ are found in the serum as a result of cardiac arrest rather than something more brain-specific, such as a stroke. I believe this speaks to Aβ (or at least some fragment of APP) being a hypoxia adaptation molecule, and it could perform this function body-wide, in addition to in the brain. It’s also important to note that oxygen levels in the brain can drop with aging as cerebral blood flow decreases, which could drive production of Aβ as an adaptation.
The University of Adelaide
I agree with Kim Green. My lab recently showed that the upregulation of the genes required for Aβ production (APP, PSEN1, PSEN2, and the γ-secretase-dependent upregulation of BACE1, as observed under hypoxia in human cells) has been conserved in zebrafish, i.e., since the divergence of these lineages approximately 400 million years ago. Thus, these genes appear to be involved in a highly conserved (and thus selectively advantageous/protective) response to low oxygen. See the reference below.
References:
Nik SH, Wilson L, Newman M, Croft K, Mori TA, Musgrave I, Lardelli M. The BACE1-PSEN-AβPP Regulatory Axis has an Ancient Role in Response to Low Oxygen/Oxidative Stress. J Alzheimers Dis. 2011 Nov 1; PubMed.
Faccultad de medicina
I think this is a wonderful study. It shows us a strong relation between oxygen and Aβ. We can also study what happens with people living at a high elevation, such as the people in La Paz. Is there more Alzheimer's disease there? Or would adaptation to low oxygen lead to less production of Aβ? It will be interesting to me to see if APP is a hypoxia protein molecule, or if Aβ is induced after hypoxia.
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