Same, I made it to the Nexus, saved my game, I thought, and then took a break. I came back and I had no saved files and all the settings were reset. I even watched the save icon pop up and then go away before I quit. Every time I open the game, it acts like it's the first time and has me adjust the brightness and safe zone.
I tried validating game files, reinstalling the game, and moving it to a different drive. None of them fixed it.
I had the same issue. Turned out to be my Virus Scanner protecting the folders that the game writes to from Ransomware. Once I added ME-A to the list of trusted applications, then it allowed both the settings and saves to be saved.
Maybe this could be your issue.
If you are on Xbox I could not save if I was offline, now I did not take myself offline the game just lost connection (even though I am hardwired with 100 up). That definitely would stop you from saving. If you are PC well that is for someone else.
Yeah, seems very likely an app is blocking the game from writing to the disk. Also keep in mind that the game may be saving settings and save files to users\<username>\AppData... or \Documents... rather than the main game library (I haven´t checked myself).