Look deep inside the brain of someone with Alzheimer's disease, most forms of dementia, or the concussion-related syndrome known as chronic traumatic encephalopathy (CTE) and you'll find a common suspected culprit: stringy, hairball-like tangles of a protein called tau.
Such conditions, collectively known as "tauopathies," affect tens of people across the globe, with Alzheimer's alone affecting six million people in the United States.
But more than a century after German psychiatrist Alois Alzheimer discovered tau tangles, scientists still have much to learn about them.
A University of Colorado Boulder study, published last week in the journal Neuron, shows for the first time that tau aggregates gobble up RNA, or ribonucleic acid, inside cells and interfere with an integral mechanism called splicing, by which cells ultimately produce needed proteins.
For the study, the researchers isolated tau aggregates from cell lines and from the brains of mice with an Alzheimer's-like condition. Then they used genetic sequencing techniques to determine what was inside.
They confirmed for the first time that tau aggregates contain RNA, or ribonucleic acid, a single-stranded molecule key for synthesizing proteins in cells. They identified what kind of RNA it is, specifically snRNA, or small nuclear RNA, and snoRNA, or small nucleolar RNA.
They also discovered that tau interacts with pieces of cellular machinery known as nuclear speckles, sequestering and displacing proteins inside them and disrupting a process called RNA splicing in which the cell weeds out unneeded material to generate new, healthy RNA.
"Understanding how tau leads to neurodegeneration is the crux of not just understanding Alzheimer's disease but also multiple other neurological diseases. If we can understand what it does and how it goes bad in disease we can develop new therapies for conditions that now are largely untreatable," said Roy Parker, senior author, and director of the BioFrontiers Institute at CU Boulder, in a report published on the university's website. "There is nothing we can do for these patients right now - no disease modifying treatments for Alzheimer's or most of the other tauopathies," he added.
