In dealing with complex things like ourselves, analogies help me a lot. I would offer two for comment and correction, partly because I would like to know if they are correct...

First, the blood brain barrier is like a lady's elbow length glove. Her arm is the vein or artery, her fingers the capillaries. If she interlocks the fingers of her two hands then one arm is a vein and the other is an artery. Her gloves separate one region (her) from another (the world).

In general, her glove acts to keep larger things from passing through while allowing smaller things to pass. THe tightness of the weave determines this and that tightness fluctuates. If the glove gets wet, for example, or is stretched.

Second, the concept of the role of genes and PD. Think of each of us as a variation of a piece of music inscribed on an old player piano roll. While we are not exactly alike, anyone who heard our particular variation would be able to recognize the piece of music. Each note is defined by a hole in the paper strip and sounds out as it goes by. The role is a continuous band and plays until it breaks from wear or weakness.

The role is our DNA and each hole is a gene. The piece of music is "human" and each is different and yet the same. Sometimes, however, individual notes can be way off or missing entirely, and the discordance can be jarring. Illness can result.

Now, if you wil picture yourself standing in the open doorway of an oldtime music hall. Down front the player piano is chugging away with its particular version of the paper role. But there are many other sounds, too. The din of conversation, the clink of glasses. From outside the traffic in the street, a distant clock chimes, etc. All these combine to create what we are. The hole passes and the gene expresses and then goes quiet until its next pass. Perhaps it is a little out of place and is not noticeable in the noise of the hall. Or perhaps it comes by just as a lull in conversation descends and suddenly is noticed.

Disease (PD or otherwise) can result from the coincidental misplaced hole pairing with the random lull. There would be many opportunities for such things to happen but the odds are always low unless the hole is very much out of place.

The more holes out of place, the amount they are displaced, the pattern of the other sounds, the time of day at the hall, the nature of the crowd, etc all combine to determine whether the net result is a ragtime favorite or PD. The BBB may fail, but that is the mechanism, not the cause. The genes may be misplaced, but that alone is not enough. In fact, no ONE thing is enough.

The old saying of "many paths to the same door" is apropriate here.