Alzheimer Nitric Oxide NOS2

[orion98665]

Abstract:
Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that demonstrates a full spectrum of characteristic Alzheimer disease–like pathologies. This model demonstrates an altered immune redox state reminiscent of the human disease and capitalizes on data indicating critical differences between human and mouse immune responses, particularly in nitric oxide levels produced by immune activation of the NOS2 gene. Using the APPSwDI+/+/mNos2−/− (CVN-AD) mouse strain, we show a sequence of pathologic events leading to neurodegeneration,which include pathologically hyperphosphorylated tau in the perforant pathway at 6 weeks of age progressing to insoluble tau, early appearance of β-amyloid peptides in perivascular deposits around blood vessels in brain regions known to be vulnerable to Alzheimer disease, and progression to damage and overt loss in select vulnerable neuronal populations in these regions. The role of species differences between hNOS2 and mNos2 was supported by generating mice in which the human NOS2 gene replaced mNos2. When crossed with CVN-AD mice, pathologic characteristics of this new strain (APPSwDI+/−/HuNOS2tg+/+/mNos2−/−) mimicked the pathologic phenotypes found in the CVN-AD strain.

http://journals.lww.com/jneuropath/Full ... _in.4.aspx

Lengthy article that i haven't read completely but very interesting..!!! So what do you think..???

Bob

[cheerleader]

Hi Bob--

Inducible (iNOS) nitric oxide is considered a bad guy in Alzheimer's---in fact, its presence is a sign of endothelial dysfunction, and is linked to many diseases. But iNOS--what is discussed in the paper you linked, because it has been induced-- is different than endothelially derived NO or eNOS, which is the form of nitric oxide referred to as a marker of vascular health, and is created by the endothelial cells. Here's a paper explaining the difference. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905037/ And yes, mouse and human reactions are different. There is most certainly an involvement of blood vessels in Alzheimer's and all diseases of neurodegeneration---note the connection to perivascular deposits.

But why is iNOS turned on in the brain? I sat down with Dr. Paula Grammas, a neurovascular biologist, Alzheimer's specialist and keynote speaker at the ISNVD--she explains what is going on in human brains in Alzheimer's (not just mice) and how the blood vessels and endothelium are involved. She also has some suggestions for maintaining brain health---and it's all in plain English
Here's our talk:


Hope it helps!
cheer