Table 2 Outstanding questions
From: Atherosclerosis and Alzheimer - diseases with a common cause? Inflammation, oxysterols, vasculature
1 | What is the molecular target for 25OHC? |
2 | Does the 'immunosterol' 25OHC also have anti-pathogen effects against bacteria and parasites? |
3 | Do other immunosterols, including 27OHC, 24(S)OHC, 24(S),25-epoxycholesterol, as well as derivatives of cholesterol precursors, operate by the same or different pathways? Do they confer protection to different types of pathogens? |
4 | How does APOE modulate infection? Is there a specific interaction between different polymorphic forms of APOE and oxysterols including 25OHC (or does it act via a partner such as APP/Aβ cholesterol oxidation)? |
5 | Is Aβ production a cause of disease, or is it a defense mechanism? |
6 | Does infection/inflammation in brain microglia also upregulate CH25H expression? |
7 | How do we explain the 'APOE paradox' – that APOE4 is associated with highest risk of both AD and ATH, but Apoe knockout in mouse models accelerates ATH but delays AD development. |
8 | How do we explain the striking age-related increase in both AD and ATH incidence? Is it due to lifetime changes in circulating steroids/sterols? |
9 | Are other age-dependent diseases caused by a similar infection/inflammation/occlusion cascade? |