At approximately 4.15am, the woman was seen walking between junctions 5 and 4B eastbound towards London.
The M4 eastbound was closed for several hours for investigation work, but has now re-opened.
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Senior Investigating Officer Sergeant Matt Cadmore of the Joint Operations Roads Policing Unit, based at Taplow, said: “This was a tragic incident which has very sadly resulted in the death of a female pedestrian.
“I am appealing to anybody who was driving on the M4 at around the time of the collision to please check their dash-cam footage and contact Thames Valley Police if it has captured anything that can assist this investigation.
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“I would also urge anybody who saw the female on the carriageway in the moments leading up to the collision, or who witnessed the incident, to please get in touch.
“You can do so by calling 101, or report online, quoting incident reference number 0200 of 27 January.
“Enquiries are ongoing to identify the victim’s next of kin, and that remains one of our top priorities at this time.”