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Probably the most interesting matchup this afternoon will be the Eagles potent run attack vs the 49ers stingy run defense. The Eagles currently have the top rushing attack in the NFC (2nd in the NFL) and before you think that's all due to having Michael Vick... LeSean McCoy is currently second in the league in rushing with 345 yards.
On the other side, Niners sport the leagues third best rush defense allowing only 62.7 rush yards per game. The spread between what the Niners give up and what the Eagles gain this year is nearly 115 yards. So obviously something has to give.
Against the pass however, the 49ers are nothing special and they don't rush the passer particularly well. That would seem like a mismatch against this Eagles team, but the fact is that the Eagles vaunted pass attack hasn't really shown up this year. They sit 20th in the league in pass yards per game. So if the Eagles can get DeSean Jackson and the pass game rolling, it could be where this game is decided.
As for the Eagles defense vs 49ers offense... We all know the struggles the D has had, but the Niners are dead last in the NFL in terms of yards per game. They don't run or throw the ball particularly well and rank in the bottom five of the league in both categories. Alex Smith has been sacked the third most times in the league so far. So if there's ever a week where this defense can get some confidence and put a solid performance out there, it's this week.