Dementia Biomarkers 101: What is Tau—and Will It Define the Next Generation of Alzheimer’s Drugs?


Possibly you’ve heard of amyloid plaques, which construct up within the brains of individuals with Alzheimer’s. However there’s one other protein biomarker within the combine: tau, which tangles round neurons. Drug firms are engaged on new medicine to assist clear these tangles and deal with the illness.

When Alois Alzheimer first studied the postmortem brains of sufferers who died with progressive reminiscence issues within the early 1900s, he noticed a buildup of beta-amyloid plaques and tau tangles. This illness was later named after its discoverer. 

For many years afterward, researchers had centered on beta-amyloid plaques, which construct up within the brains of Alzheimer’s sufferers early within the illness. However comparatively talking, they didn’t pay a lot consideration to tau. 

In consequence, many Alzheimer’s medicine — like the brand new monoclonal antibodies for Alzheimer’s — have been developed to attempt to clear amyloid plaques.

Via medical trials, scientists discovered that clearing amyloid plaques doesn’t fully clear up the issue. Even amyloid plaque-busting medicine like Leqembi and Aduhelm solely slowed cognitive decline a small bit. Within the final decade, they’ve additionally found that tau does a greater job of predicting Alzheimer’s illness development and would possibly even be a extra correct blood-based biomarker of the illness. 

In the meantime, comparatively few drug builders have set their sights on tau — till now.

What’s tau?

Tau sticks to the interior skeleton of mind cells, serving to stabilize these necessary buildings. The skeleton works like a bridge connecting totally different elements of the cell, whereas the tau proteins act just like the trusses and different helps that preserve the bridge secure and standing. 

When wholesome, tau stabilizes these mobile bridges, permitting it to move vitamins, chemical alerts, and different items all through the cell.

However what occurs when the helps holding up the bridge begin to fail? When tau turns into misfolded, it stops sticking to the bridge and as an alternative begins sticking to different tau proteins, forming what researchers name tau or neurofibrillary tangles. The tangles disrupt wholesome mobile operate because the bridges that preserve the cell wholesome collapse. 

Some research discover that tau could be a biomarker of Alzheimer’s, however tau tangles aren’t a singular pathology. Bruno Imbimbo, a researcher and Alzheimer’s drug developer on the pharmaceutical firm Chiesi Farmaceutici, informed Being Affected person that additionally it is related to different neurodegenerative illnesses as effectively — like frontotemporal dementia and progressive supranuclear palsy.

Can clearing tau tangles deal with Alzheimer’s?

Might anti-tau medicine — antibodies sticking to tau tangles and serving to the mind’s immune system clear them out — assist deal with Alzheimer’s illness? We don’t have the reply but. However, scientists assume that tau tangles could be concerned in Alzheimer’s development and signs. 

“It’s unlikely you can take away the tangles however you may take away the sooner tau pathology which is able to seemingly enhance cognition or sluggish cognitive deterioration as a result of tau pathology correlates with cognitive decline,” Einar M. Sigurdsson, a professor at NYU Langone Well being informed Being Affected person. “This will even stop new tangles from forming.”

However Imbimbo cautioned that we nonetheless aren’t positive “whether or not neurofibrillary tangles are a main reason for Alzheimer’s illness.” 

One thing else would possibly trigger Alzheimer’s, and these plaques would possibly happen by the way.

Are there medical trials for anti-tau antibodies?

If scientists have realized something from growing anti-amyloid antibodies, success gained’t come straightforward. Imbimbo thinks the highway can be “lengthy and may very well be tough.” To date, scientists have examined 11 anti-tau antibodies in sufferers. And to date, most have failed to indicate promise in medical trials. 

Imbimbo defined that these antibodies solely follow tau discovered floating within the cerebrospinal fluid however don’t truly goal the elements of the protein that tangle up and wreak havoc inside mind cells.

He defined that new medicine are being developed that may get inside mind cells and goal the sticky elements of the tau proteins to unclump a number of the tangles. The antibodies may trigger clumps of tau to interrupt aside and stop a number of the mind cells from dying.

Two of those newer anti-tau medicine have already gone via preliminary Section 1 trials. Jannsen is presently working a Section 2 trial of its anti-tau antibody JNJ-63733657 in early Alzheimer’s illness. The trial is slated for completion on the finish of 2025. 

Drug firm Prothena can also be growing anti-tau antibodies and lately licensed PRX005 to Bristol Myers Squibb who will conduct a Section 2 trial within the close to future.

Ought to we goal amyloid, tau, or one thing else?

Alzheimer’s is a fancy illness, and scientists are nonetheless debating its precise trigger. However having a number of therapies for a similar illness may very well be useful, particularly when some individuals are extra vulnerable to unintended effects from one of many therapies.

An anti-tau antibody could also be safer than an anti-amyloid antibody, Sigurdsson stated, as a result of it gained’t trigger mind bleeds (ARIA) as a facet impact. These bleeds are a facet impact of anti-amyloid remedy that happens when antibodies follow amyloid that’s constructed up on blood vessels, inflicting them to burst. “Tau antibodies have been secure in medical trials with no apparent unintended effects,” he stated. 

Anti-tau antibodies or some other singular drug alone are unlikely to resolve Alzheimer’s illness. 

“I believe it’s naive to assume we’ll get the tablet for Alzheimer’s,” Dr. Donald Weaver, a now-retired medical neurologist and former director at Krembil Institute, informed Being Affected person. “Furthermore, we don’t know if Alzheimer’s is one illness or many separate entities.”  

He likens treating Alzheimer’s to different advanced circumstances like hypertension — which include many various causes. Folks take totally different medicine relying on what’s inflicting their blood strain to spike, and sooner or later, folks would possibly take particular Alzheimer’s medicine relying on their particular person pathology.