Specifically, a member of the alien species written about by H. P. Lovecraft in his story, The Colour Out of Space. The way the Usher's property turned blighted and the way madness crept into their family greatly resembles the way The Colour affected the Gardner family after landing on Earth. The Colour that affects the Ushers, however, seems to be of a less virulent strain, taking decades, even centuries to fully manifest. The main seat of its power seems to be the tarn under the Usher House, which it has overtaken, spreading itself outwards towards the surrounding lands, and turning the House above it into an almost living entity. The Blight affecting the Ushers grants them acute senses and super strength and is sexually transmissible (which may be why the Ushers intermarried in order to keep it in the family—and is why Roderick is desperately trying to see that it dies out.) The reason the house collapses at the end could be because the Blight was at the end of its life cycle, or was trying to generate enough energy to shoot itself back out into space (like The Colour did at the Gardner farm.) In any case, whatever it was appeared to have died by the end of the story.
- Building on this, rather than expressing itself as an unknown colour, the main visible effect of the less virulent Usher blight was draining the colours of the organisms it infected.
The symptoms of the Usher siblings are consistent with ionizing radiation poisoning: weakness, fatigue, confusion, sensitivity to light, hair loss, and pale skin (caused by frequent replacement thereof) are all symptoms of excessive radiation exposure. It is mentioned that physicians were mystified, which makes sense, as radioactivity was not even known to exist at this time.
The poem suggests the cause of this chain of events: that at some point in the last few hundred years, possibly connected to excavations under the house (as suggested by Usher's painting), an outlet to the surface from some deposit of uranium ore was formed, leading to radon seeping upward and triggering the decline (although not causing it, as the radioactivity wouldn't have been that effective - more likely a positive feedback thing). The crack across the front of the house also suggests this.
The strongest evidence for this theory is this passage:
"But the under surfaces of the huge masses of agitated vapor, as well as all terrestrial objects immediately around us, were glowing in the unnatural light of a faintly luminous and distinctly visible gaseous exhalation which hung about and enshrouded the mansion.
You must not you shall not behold this! said I, shudderingly, to Usher, as I led him, with a gentle violence, from the window to a seat. These appearances, which bewilder you, are merely electrical phenomena not uncommon or it may be that they have their ghastly origin in the rank miasma of the tarn. Let us close this casement; the air is chilling and dangerous to your frame. [italics added]"
It's not even impossible that this is what Poe intended. Although the cause of the phenomenon would not have been known, it could have become folklore, as the correlation was noticed, that people who spent a lot of time in cellars and mines developed these types of problems and/or lung cancers more frequently. Poe may have heard such stories, and either deliberately tried to cultivate an association in the story between these phenomena and dark, dank, creepy mines and tunnels underground, or made the connection subconsciously.