The "spread" in this context always means the difference between your exercise price and the fair market value of the stock on the date of exercise. For example, you hold ISOs for which you can buy common stock at $.10/sh. You exercise them when the stock is worth $1.00/sh. The spread is the $.90 difference. (If this exercise involved 100K shares, the amount potentially includable in AMT would be $90K).
409A is an arbitrary (in my view) tax rule that imposes large penalties if a company undervalues items that are given as "deferred compensation" to employees. It is not affected by the spread on date of exercise but rather by the way a board values options on date of grant (to avoid penalties, a company must get an independent, outside appraisal of its stock in setting such a valuation - in practical terms, this becomes an issue typically after a first equity funding because, before that, there usually is no serious practical risk of the IRS being able to put an objective measure on the stock's value in an early-stage company so as to have a basis upon which to attempt to impose penalties).
As to Question 2, I normally urge people to strike a balance - the advantages of getting LTCG treatment justify taking moderate risks for most employees but don't do it if you have to part with a lot of cash and if you have to take AMT hits even if you do believe in the company (in my experience, it is too easy to get blind-sided in this area, no matter how promising a typical startup looks; more yet, option holders do ride the caboose when it comes to liquidity events and can sometimes lose even if the company wins). Bottom line: front-exercise if possible but always proceed with caution and only after you understand all the issues well (including tax).