Protein Breakthrough That Could Transform Dementia Diagnosis

A newly identified age-related dementia (LATE dementia) often co-occurs with the symptoms of Alzheimer's disease.

What is LATE Dementia

LATE dementia is scientifically called as Limbic-predominant age-related TDP-43 encephalopathy, according to research by Jijing Wang, PhD, and Hyun-Sik Yang, MD, of the Department of Neurology at Mass General Brigham (1^✔ ✔Trusted Source
Plasma TDP-43 is a potential biomarker for advanced limbic-predominant age-related TDP-43 encephalopathy neuropathologic change

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The paper was published in Molecular Neurodegeneration.

The study discovered that a specific protein, known as TDP-43, which buildup in the brain of LATE dementia people, is detectable in blood.

Also, the study confirms that individuals with age-related LATE dementia had higher blood TDP-43 protein along with the presence of Alzheimer's.

The findings open door for better targeted treatments and clinical trials for a good public health outcome.

Linking Blood Samples to Brain Autopsies

While Alzheimer’s disease can now be diagnosed during life using blood or spinal fluid tests, LATE – another important cause of memory loss – can only be confirmed through a brain autopsy.

The research aimed to address this major gap in dementia research by investigating whether the TDP-43 protein could represent a viable biomarker to reveal the presence of LATE in living individuals.

Scientists analyzed plasma samples from 50 participants in the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), a well-established research cohort based at Rush University Medical Center in Chicago.

The samples were collected several years before these older adults passed away and donated their brains to research.

Strongest Association When Dementia Co-exists with Alzheimer's

Using an ultra-sensitive test, researchers measured the amount of total and phosphorylated, or chemically-modified, TDP-43 in their blood samples, then compared these blood levels with the extent of disease observed in their brains at autopsy.

It was found that people with advanced LATE disease had significantly higher amounts of TDP-43 in their blood, particularly if they also had brain changes from Alzheimer’s disease.

Scientists also discovered that both forms of TDP-43 that we measured in blood closely reflected how much of this protein had built up in the brain at autopsy. Importantly, these relationships stayed strong even after we accounted for other brain changes linked to Alzheimer’s disease, including amyloid and tau proteins.

Advancing Dementia Diagnosis Through Blood Test

These findings are exciting since they suggest that a simple blood test could eventually help identify LATE during life, particularly in those who also have Alzheimer’s disease.

Identifying a reliable blood biomarker like this would make it possible to distinguish between different causes of dementia, and would represent an important step toward better diagnosis and treatment.

While the findings are promising, larger and more diverse studies are needed to confirm these results and test whether blood TDP-43 can also detect LATE in people who don't have Alzheimer’s disease.

It will also be important to determine whether changes in blood TDP-43 levels can track disease progression over time. The long-term vision is to incorporate TDP-43 into a blood-based toolkit to improve early detection, refine clinical trial design and advance our understanding of dementia beyond Alzheimer’s disease.

Reference:

1. Plasma TDP-43 is a potential biomarker for advanced limbic-predominant age-related TDP-43 encephalopathy neuropathologic change - (https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-025-00910-4)

Source-Eurekalert