Midway through the first half, Steven Bergwijn broke through into the United box and fired a strike straight at De Gea, who allowed it to bounce off a weak hand and into the roof of the net, giving Spurs the lead.
United would go on to eventually draw 1-1, but most of the headlines surrounded the Spanish keeper and the major criticism he received, most notably on Sky's coverage of the match from former midfielder Roy Keane.
Although Neville was not as vicious with his criticism as Keane, who said he would be “throwing punches” in the United dressing room, the Sky Sports pundit admitted to being concerned at the form of De Gea, which he believes has been declining for too long.
"He was the one player United could rely upon for the last four years but he's not the same," he said on The Gary Neville Podcast.
"He hasn't been the same for some time. When form drops for six months it's a blip but when it goes on for a year you start to worry. When it goes over two years it becomes more permanent.
"That is now a fair representation of what De Gea is as he's making lots of mistakes. Ones he would never make - he was always somebody you could completely rely upon. It can only be a confidence thing. The arms, legs and body are the same - it's got to be the mind.
"The reception he's got in Spain has affected him. He's even been booed by Spanish fans when he's wearing the Spanish shirt. In the World Cup in 2018 he really struggled and from that he's doubted himself. Mentally he's not quite the same. He's got to go back to basics.”
The former United captain believes only hard work will ultimately pull De Gea out of his current malaise.
He added: "There's only one thing you can do when you're having a tough time: work. Work harder than you have ever done in your life. What will happen is that you will tell yourself the amount of work you put in you deserve to be good again. That means coming in at 7.30am and leaving at 6pm if needs be. He has to do something to stop the erosion.
"Mistakes like that can happen on the first game back but it's happening far too much over the past couple of years."