Scientists Discover a Common Thread That Causes Neurodegenerative Disease

A cell-by-cell examination of a brain affected by Alzheimer's disease revealed microscopic aggregates of protein that appear suspicious.

Researchers have discovered that additional brain illnesses have their tangled-protein fingerprints since the 1980s when neuroscientists began recognizing these protein tangles.

Protein that causes neurodegenerative disease

Each of these diseases has a distinct protein tangle, or fibril, associated with it, according to Anthony Fitzpatrick, Ph.D., principal investigator at Columbia's Zuckerman Institute, as well as an assistant professor of biochemistry and molecular biophysics at Columbia University Irving Medical Center and a member of Columbia's Taub Institute for Research on Alzheimer's Disease and the Aging Brain.

In a report by ScienceDaily, they discovered that a protein called TMEM106B may form fibrils, which was previously unknown, according to Xinyu Xiang, a former Fitzpatrick lab member at the Zuckerman Institute and currently a doctoral student at Stanford University's Department of Structural Biology.

This protein is a necessary component of lysosomes and endosomes, which are organelles that clean up the debris that accumulates in our cells as we age.

TMEM106B molecules normally cross the membranes of these waste-management organelles.

Fitzpatrick's team revealed that TMEM106B molecules may divide into two pieces in a feat of scientific sleuthing.

Fragments within the organelles can then self-assemble into what researchers believe are cell-hobbling fibrils.

This valuable research resource was obtained with the assistance of co-corresponding author Ian Mackenzie, MD, of the University of British Columbia, and co-authors Dennis Dickson, MD, and Leonard Pertrocelli, Ph.D., of the Mayo Clinic in Florida.

Along with Drs. Michael Stowell, Ph.D., of the University of Colorado, Boulder, are co-corresponding authors on the work with Fitzpatrick and Mackenzie.

Researchers from a variety of other universities, including three from Belgium, round out the 23-person team.

The scientists used a world-class cryogenic electron microscope (cryo-EM) to capture images of individual protein molecules from a variety of angles.

The researchers used these to create three-dimensional models of the enzyme in microscopic detail. These models, in turn, assisted the researchers in identifying TMEM106B by generating informed assumptions about the precise sequence of the protein's amino-acid building blocks, as per Columbia Zuckerman Institute.

Similar to how letters tie together to form words with unique meanings, various amino-acid molecules combine to form proteins, within each shape and function.

The role of tau in neurodegenerative disease

According to News Medical, researchers from the Buck Institute and others have mapped the "tau interactome" using cutting-edge proteomics, revealing new insights into the function of tau in neurodegenerative illness.

Scientists discovered that mutant tau affects mitochondrial activity in human neurons in a study published in Cell.

They also propose a mechanism for tau release from neurons and dissemination across the brain, a degenerative process strongly linked to disease development.

Normal tau is well with its role in attaching to microtubules which are responsible for the cell's cytoskeleton.

In illness, aberrant chemical changes cause tau to detach from microtubules and attach to other tau proteins, generating threads that eventually unite to create tangles inside neurons.

The presence of tau tangles is one of the hallmarks of Alzheimer's disease and associated tauopathies.

Alzheimer's disease, degenerative supranuclear palsy, Pick's disease, chronic traumatic encephalopathy, frontotemporal dementia, corticobasal degeneration, and post-encephalitic parkinsonism are all clinical-pathological phenomena classified as tauopathies.