A diagnostic biomarker that can identify fatal brain diseases with high accuracy

Focusing on one disease and studying it in depth is often the most effective way
to find a cure.
However, because the symptoms are so similar, it can be difficult to distinguish between people
with primary psoriasis.
Psoriasis is a rare group of brain disorders characterized by rapid deterioration
of thinking and motor problems.
As a result, most studies on primary psoriasis include a mix of these diseases, although researchers know that these diseases differ in important ways and may require different treatments
.

Now, however, researchers at Washington University School of Medicine in St.
Louis have discovered a biomarker that can identify patients with primary psoriasis known as cortical basal degeneration (CBD) with up to 89 percent
accuracy.
Researchers say that traditional CBD diagnostic methods are only 25 to 50 percent accurate
.

The scientists say the biomarker could be developed as a tool for screening potential volunteers, conducting studies and clinical trials against CBD, and ultimately identifying those who could benefit from CBD-specific treatments
.

Dr Chihiro Sato, assistant professor of neurology and senior co-author, said: "Previously, the only way to find out which primary psoriasis a person had was to wait until after he died and then examine his brain
under a microscope.
" "Patients have stiffness, balance problems, slurred speech and memory problems, which could be CBD, but it could also be progressive supranuclear palsy (PSP) or Alzheimer's or something else
," he said.
This biomarker can reliably identify people with CBD, which means we can use it to recruit patients to participate in clinical trials
.
And, in the future, this could be the key to
initiating treatment.
”

CBD is one of more than two dozen brain diseases considered to be shea butter because they share a key feature: the toxic tau protein accumulates
in the brain.
Individual tau disease involves different tau subtypes and exhibits different patterns of brain cell and tissue damage
.
The overlapping collections of symptoms of various psoriasis diseases make it difficult for doctors to distinguish
.
This complicates
the study of them and the search for cures.

Tau disease can be classified as primary or secondary, depending on when the tau tangles appear during the course of the disease
.
In primary psoriasis, tau protein tangles form at the beginning and appear to form
on their own.
In secondary psoriasis, tangles form
only after other changes in the brain.
For example, in Alzheimer's, the most common secondary psoriasis, amyloid β in the brain accumulates for years
before tau protein tangles appear.

In 2020, Kanta Horie, Ph.
D.
, associate professor of neurology research and first author of the paper, developed a highly sensitive technique for detecting specific tau protein fragments
in the brain and perispinal cerebrospinal fluid.
Horie and his colleagues used this technique to identify a novel tau protein in Alzheimer's patients and showed that levels of this new tau protein in the cerebrospinal fluid indicate the stage of the disease and coincide with
the number of tau tangles in the brain.

As part of the study, Horie, Sato and colleagues — including co-senior authors Randall J.
Bateman, M.
D.
, Charles F.
and Joanne Knight Distinguished Professor of Neurology — used the technique to look for a unique form of
tau protein associated with primary psoriasis 。 To ensure accurate classification of the study subjects, Horie Sato and Bateman collaborated with co-authors Adam Boxer, M.
D.
, Salvatore Spina, M.
D.
, and Lawren Vande Vrede, M.
D.
, all from UCSF's Department
of Neurology.
The team examined brain tissue and cerebrospinal fluid from patients who died of dementia and dyskinesia, whose specific diseases were confirmed
at autopsies.
The study population included patients with one of five primary psoriasis; frontotemporal degeneration with microtubule-associated protein tau mutation (FTLD-MAPT); Estrogenic granulopathy; Pick's disease, as well as Alzheimer's disease and dementia unrelated to tau
.
For comparison, they also examined samples
from people without dementia.

Two special forms of tau protein-microtubule-binding region (MTBR)-tau protein 275 and MTBR-tau protein 282 were abnormally high in cerebrospinal fluid and abnormally low
in cerebrospinal fluid in CBD and FTLD-MAPT patients.
Further studies have shown that depending on the disease, these tau protein forms can distinguish CBD patients from other primary psoriasis patients with 84% to 89%
accuracy.

"Even if there is an experimental drug that specifically targets the tau protein in CBD, it is very challenging to test it without biomarkers
.
" "If the population is heterogeneous, trials can fail
even if the drug is effective.
Drug trials that specifically target tau protein in CBD can be improved
by recruiting patients with the correct diagnosis.
Having a biomarker opens up a pathway for pharmaceutical companies to improve clinical trials and accelerate research
into CBD therapeutics.
”

Several experimental drugs targeting tau protein are in development
.
Most are designed for Alzheimer's patients, but they may be an effective treatment
for primary psoriasis.
The researchers say Horie's technique could be used to look for other biomarkers of primary psoriasis, opening the door
to more clinical trials.

"CBD patients and families desperately need effective treatments, but organizing clinical trials for this deadly disease has been challenging
.
" "Until now, we didn't have a specific biomarker to accurately diagnose patients
.
This new biomarker also opens the door to testing many new ceramic protein-targeted CBD therapies, as it may allow us to directly measure the ability
of these therapies to reduce toxic ceramic protein levels in a patient's brain.
”