Five biomarkers for four neurodegenerative diseases

Five proteins (SPC25, NEFL, S100A13, TBCA, and LRRN1) were found in people with Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS), and allowed high accuracy (AUC 0.90–0.96) prediction of the presence of the APOE e4 variant, one of the main genetic risk factors for senile dementia.

APOE e4 has long been considered an important risk marker for late-onset Alzheimer’s disease, but it does not cause the disease by itself. Moreover, the key culprits — such as amyloid plaques and tau protein — also, as it turns out, do not explain everything. Therefore, the search for universal molecular features continues.

Almost 19,000 people participated in the new study, and data was collected in 23 countries, including plasma, serum, and cerebrospinal fluid samples. Scientists have found hundreds of differences in the protein composition of blood in different diseases:

• in Alzheimer’s disease, disorders of glucose metabolism and transport proteins;
• in Parkinson’s disease, changes in Ras protein signaling pathways;
• in frontotemporal dementia, a decrease in synaptic proteins;
• in ALS, there are pronounced muscle protein markers.

But through all this diversity, there is one common signal — the five-protein profile associated with APOE e4, which is equally evident in all four diagnoses.

Although these data are still correlative (that is, without a proven causal relationship), such a common molecular pattern is an important step towards creating universal diagnostic tests and finding new treatment targets. Such biomarkers make it possible to detect diseases at an early stage, before symptoms appear, and track their progression.

In addition, the researchers used the LASSO model on 256 proteins to track the clinical severity of diseases, as well as the “clock of the organs” of aging. It turned out that with Alzheimer’s, the aging of the arteries, liver and intestines accelerates, and with Parkinson’s— skeletal muscles.

A common biomarker for four neurodegenerative diseases is a crucial clue for future treatments and diagnostics. The way to defeat brain aging is through international science.