A shared five biomarker profile across four major neurodegenerative diseases

The Global Neurodegeneration Proteomics Consortium (GNPC) has published a series of research papers detailing their efforts to identify patterns in neurodegenerative disease. Sifting through roughly 250 million plasma measurements, they have discovered a five-protein panel present in APOE ε4 carriers across Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia and amyotrophic lateral sclerosis.

The APOE ε4 allele is a genetic variant with a strong association for increased risk of developing late-onset Alzheimer’s disease. Having one or two copies of the allele elevates the likelihood of developing the disease and experiencing an earlier onset. While it has been a clear genetic marker for risk, APOE ε4 holds no clinical value as a drug target as it has no direct causal role in the disease.

Even the much-researched suspects, amyloid and tau protein plaque build up in the brain, seem to escape full causative blame for the disease, suggesting other factors must be at work.

In one of the GNPC studies, “The Global Neurodegeneration Proteomics Consortium: biomarker and drug target discovery for common neurodegenerative diseases and aging,” published in Nature Medicine, researchers may have found the biomarkers that have eluded neurodegenerative researchers for decades.

A total of 18,645 participants contributed 31,083 plasma, serum and cerebrospinal fluid samples, yielding 35,056 unique proteomic assays drawn from 23 global cohorts.

There was plenty of variation between disease types that typical proteomic analysis would identify as significantly divergent disease drivers.

Plasma analyses identified 27 proteins consistently elevated and 130 reduced in Alzheimer’s disease across up to 10 cohorts, enriched for glucose metabolism and vesicle-trafficking pathways.

Parkinson’s disease samples showed 40 elevated and 15 reduced proteins, with enrichment for Ras-family GTPase signaling.

Frontotemporal dementia profiles revealed nine decreased synaptic-linked proteins, while amyotrophic lateral sclerosis signatures were dominated by skeletal-muscle proteins.

A 256-protein LASSO model tracked clinical severity across diagnoses, and organ-specific aging clocks disclosed accelerated artery, liver and intestine aging in Alzheimer’s disease and muscle aging in Parkinson’s disease.

Hidden within the protein diversity of disease manifestations, was a signal that tied all of these different profiles together. A five-protein panel (SPC25, NEFL, S100A13, TBCA, LRRN1) predicted APOE ε4 status with area under the curve 0.90–0.96 independent of diagnosis. Accuracy held, returning similarly strong AUC values across Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia and amyotrophic lateral sclerosis.

All of the findings from GNPC so far are correlative biomarker signals. No mechanistic experiments or causal inferences are being presented and causality remains unclear.

These disclaimers and caveats aside, a previously unknown biomarker profile shared across multiple neurodegenerative diseases is exactly the sort of clue that researchers have been needing to pursue disease-modifying strategies.

According to Bill Gates, the principal founder of GNPC, “This is the moment to spend more money on research, not less. And this is the time to encourage more collaboration across borders, not less. The rising tides of nationalism and isolationism threaten to stop scientific progress in its tracks, and I hope countries reverse course before we lose too much ground.”

Gates frames this call for cross-border scientific cooperation by pointing to some recent global success stories: “Some of the biggest medical discoveries of the past half-century were made possible through global partnerships. The Human Genome Project—a joint venture by the U.S., UK, Japan, France, Germany and China—paved the way for precision medicine and genetic testing.

“We have a vaccine against human papillomavirus, the leading cause of cervical cancer, because research teams in the U.S. and Australia built on the discoveries of a German scientist. And, most recently, it took unprecedented levels of global cooperation to develop vaccines against COVID-19 in record time.”

© 2025 Science X Network

The Global Neurodegeneration Proteomics Consortium (GNPC) has published a series of research papers detailing their efforts to identify patterns in neurodegenerative disease. Sifting through roughly 250 million plasma measurements, they have discovered a five-protein panel present in APOE ε4 carriers across Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia and amyotrophic lateral sclerosis.

The APOE ε4 allele is a genetic variant with a strong association for increased risk of developing late-onset Alzheimer’s disease. Having one or two copies of the allele elevates the likelihood of developing the disease and experiencing an earlier onset. While it has been a clear genetic marker for risk, APOE ε4 holds no clinical value as a drug target as it has no direct causal role in the disease.

Even the much-researched suspects, amyloid and tau protein plaque build up in the brain, seem to escape full causative blame for the disease, suggesting other factors must be at work.

In one of the GNPC studies, “The Global Neurodegeneration Proteomics Consortium: biomarker and drug target discovery for common neurodegenerative diseases and aging,” published in Nature Medicine, researchers may have found the biomarkers that have eluded neurodegenerative researchers for decades.

A total of 18,645 participants contributed 31,083 plasma, serum and cerebrospinal fluid samples, yielding 35,056 unique proteomic assays drawn from 23 global cohorts.

There was plenty of variation between disease types that typical proteomic analysis would identify as significantly divergent disease drivers.

Plasma analyses identified 27 proteins consistently elevated and 130 reduced in Alzheimer’s disease across up to 10 cohorts, enriched for glucose metabolism and vesicle-trafficking pathways.

Parkinson’s disease samples showed 40 elevated and 15 reduced proteins, with enrichment for Ras-family GTPase signaling.

Frontotemporal dementia profiles revealed nine decreased synaptic-linked proteins, while amyotrophic lateral sclerosis signatures were dominated by skeletal-muscle proteins.

A 256-protein LASSO model tracked clinical severity across diagnoses, and organ-specific aging clocks disclosed accelerated artery, liver and intestine aging in Alzheimer’s disease and muscle aging in Parkinson’s disease.

Hidden within the protein diversity of disease manifestations, was a signal that tied all of these different profiles together. A five-protein panel (SPC25, NEFL, S100A13, TBCA, LRRN1) predicted APOE ε4 status with area under the curve 0.90–0.96 independent of diagnosis. Accuracy held, returning similarly strong AUC values across Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia and amyotrophic lateral sclerosis.

All of the findings from GNPC so far are correlative biomarker signals. No mechanistic experiments or causal inferences are being presented and causality remains unclear.

These disclaimers and caveats aside, a previously unknown biomarker profile shared across multiple neurodegenerative diseases is exactly the sort of clue that researchers have been needing to pursue disease-modifying strategies.

According to Bill Gates, the principal founder of GNPC, “This is the moment to spend more money on research, not less. And this is the time to encourage more collaboration across borders, not less. The rising tides of nationalism and isolationism threaten to stop scientific progress in its tracks, and I hope countries reverse course before we lose too much ground.”

Gates frames this call for cross-border scientific cooperation by pointing to some recent global success stories: “Some of the biggest medical discoveries of the past half-century were made possible through global partnerships. The Human Genome Project—a joint venture by the U.S., UK, Japan, France, Germany and China—paved the way for precision medicine and genetic testing.

“We have a vaccine against human papillomavirus, the leading cause of cervical cancer, because research teams in the U.S. and Australia built on the discoveries of a German scientist. And, most recently, it took unprecedented levels of global cooperation to develop vaccines against COVID-19 in record time.”

© 2025 Science X Network