New light has been shed onto the shape shifting nature of tau molecules just before beginning to stick to itself forming larger aggregates, which may offer new disease detection strategies before it takes hold, and help to develop treatments that stabilize tau proteins before they shift shape.
The team says this finding may be a game changer which is in contradiction of beliefs that isolated tau protein has no distinct shape and is only harmful after beginning to assemble with other tau proteins to form tangles seen in Alzheimer’s patient brains.
Discovery was made after extracting tau proteins from human brains, isolating them as single proteins, when it was found that the harmful form of tau exposed a part of itself normally folded inside that causes it to stick to other tau proteins enabling tangles to be formed that kill neurons.
Billions of dollars have been spent on clinical trials on Alzheimer disease research over decades, yet this devastating disease still remains one of the most baffling worldwide, which affects upwards of 5 million people within the USA alone.
Knowledge of genesis can provide vital targets in diagnosing at earliest stage before symptoms of cognitive decline and memory loss become apparent. Development of a simple clinical test to examine patient blood or spinal fluid to detect first biological signs of abnormal tau protein is underway, and just as important efforts to develop a treatment that can make diagnosis actionable.
Recently approved Tafamidis stabilizes different shape shifting transthyretin proteins that cause deadly accumulation in the heart, similar to how tau works in the brain, so there is good cause to be cautiously optimistic working on these findings to make a similar treatment to block neurodegeneration where it begins.
The lab of Dr. Diamond has been of importance to many past tau findings such as determining it to act like a prion to spread like a virus through the brain that can form many distinct strains or self replicating structures, and had developed methods to reproduce them in lab. Newest research suggests that a single pathological form of tau may have multiple possible shapes, each being associated with a different form of dementia.
