Doctors and clinicians already rely on routine blood panels to help guide recommendations for cardiovascular health. Why don’t we do the same for neurological health? Can we measure and address age-related decline using emerging proteomic technologies, such as NULISA? 

A cholesterol test for the brain 

Popularized as the “Brain Doctor” and self-described “C-minus list celebrity,” neurologist Dr. Richard Isaacson is a pioneer in preventative neurological medicine. Aiming to make the democratization of disease diagnosis a reality, Dr. Isaacson has been actively researching neurodegenerative proteomic signatures in pre-symptomatic patients and the effects of preventive measures designed to delay onset ​(Niotis et al., 2024)​.  

“I have nothing to disclose and I believe in this technology,” Dr. Isaacson said, referring to the NULISA platform. “We’re going to try anything and everything…and now we think we know how to scale [testing and data interpretation] and make it more accessible.“ 

Dr. Isaacson’s team contributed to the Biorepository for Alzheimer’s and Neurodegenerative Diseases (BioRAND) study, which verified over 150 biomarker assays spanning multiple platforms ​(Niotis et al., 2025)​. He cautions that only FDA-validated biomarkers can be disclosed to patients in communicating test results.  

In unpublished research, many of the most powerful biomarker indicators are ratios of NULISAseq CNS Panel 120 proteins, including pTau181/Aβ42, BD-pTau181/Aβ42, and oligo-synuclein/synuclein. Intriguingly, since pTau181 is the first to appear in the tau protein hyperphosphorylation cascade, it often is a better indicator for disease prevention than pTau217.  

Dr. Isaacson prescribes “n=1 personalized interventions”, including lifestyle modifications, microdosed GLP-1 receptor agonists, statins & anti-cholesterols, anti-amyloid agents, and hormone therapies. Notably, multimodal lifestyle interventions (e.g., sleep hygiene, diet, exercise, and stress reduction) normalize biomarker ratios more consistently than drug interventions, except for hormone replacement therapy in some perimenopausal women. Improving biomarker ratios through intervention remarkably increased brain volumes as measured by MRI. Just goes to show that all you learned in junior high health class and what your doctor tells you each year are noteworthy recommendations that can positively impact your brain health. 

Biological aging clocks: development and practice 

Age is consistently a major risk factor for many diseases, especially neurodegenerative disorders like Alzheimer’s disease (AD). Therefore, efforts are focused on understanding aging and quantifying its impact on health. Enter biological aging clocks, which predict a person’s age based on their underlying biology and organs rather than a count of trips around the sun. The difference between a person’s chronological age and biological age, as indicated by these clocks, is called the “age gap.” For more background, check out our blogs on proteomic aging clocks and Alamar’s role in the 2024 Biomarkers of Aging Consortium. 

Dr. Jessica Lasky-Su of Harvard Medical School is actively evolving the development of biological aging clocks — from predicting chronological age to forecasting the onset of disease or death, and to systems aging. “We are only as young as our oldest part,” she notes. The impressive predictive power of a multiomic aging clock named “oMICmAge is currently in press at Nature Aging.” The clock combines NULISA proteomics, metabolomics, and DNA methylation data from the Mass General biobank, which contains about 100,000 blood samples. [In the meantime, you can read the preprint (Chen et al., 2023).] 

“Proteomics seems to be the best readout of aging clocks because it tells us about the biology,” according to Dr. Lasky-Su. 

Her lab is also exploring the predictive potential of autoantibodies for understanding healthspan. Autoantibodies result from external insults, such as viral infections, but they also signal the development of immune dysfunction, including immunosenescence. Using herpesvirus exposure as a proof of concept for autoantibody generation, autoantibody-based aging clocks show excellent predictive power and unexpected protective age associations with certain sex-specific autoantibodies. These protective associations are more pronounced in females — sorry, fellas.  

There is currently no ‘omic readout for autoantibody reactome profiling, but stay tuned for potential proteomic integrations of autoantibodies as this research unfolds. 

In collaboration with the Mesuthaleh Foundation, Alamar has developed its own NULISA-based proteomic aging clock, with predictive capacity comparable to that of the proteomic aging clock derived from UK Biobank data ​(Argentieri et al., 2024)​. Dr. Xiao-Jun Ma, Alamar CTO and Co-Founder, helped advance this aging clock, which used both the NULISAseq Inflammation Panel 250 and the CNS Disease Panel 120, totaling 320 unique analytes across 500 individuals. Of the 188 proteins included in the aging clock, the top contributor is CCL11 (eotaxin-1), a chemokine linked to inflammaging ​(Ivanovska et al., 2020)​. Notably, killer lectin-like receptor K1 (KLRK1, also known as NKG2D) is negatively associated with aging. Lymphocytes express KLRK1 to detect and eliminate transformed and infected cells, including senescent cells ​(Sagiv et al., 2016)​. Overall, the Alamar proteomic aging clock predicts mortality with reasonable accuracy, especially in cases of premature death before age 50. 

Proteomic aging clocks in drug development 

If you ask committee members on the Biomarkers of Aging Consortium what the primary purpose of determining biological aging clocks is, many will say it’s to anticipate clinical endpoints for therapeutic aging interventions that can be carried out within a reasonable time frame. Dr. Jonathan Wilson at Eli Lilly and Company is collaborating with Alamar to test proteomic biological age clocks in a therapeutic setting using glucagon-like peptide 1 (GLP-1) mimetics. Given the extensive and growing list of positive outcomes associated with taking GLP-1 mimetics (e.g., semaglutide) and weight loss, some scientists consider these molecules to be longevity-promoting gerotherapeutics ​(Corley et al., 2025)​.  

Over the past year, Dr. Wilson has been using Alamar’s aging clock to predict biological age in a highly characterized, diverse longitudinal cohort of obesity. His team’s ARGO® HT is named Hera, “the Star of the Show and the Goddess of all Goddesses.” As expected, the aging clock predicts a higher biological age (i.e., positive age gap) in obese individuals. Markers of interest include neurofilament light chain (NEFL) and eotaxin-1 (CCL11), in agreement with Dr. Ma’s assessment of the Methuselah data.  

In an 18-week clinical study of caloric restriction comparing placebo and tirzepatide-treated subjects, the placebo group experienced an 8% reduction in body weight, along with a decrease in the proteomic biological age gap. Importantly, signatures of response and non-response to caloric restriction were apparent, including the adipokine FGF21, which increased in individuals whose age gap widened after 18 weeks. These findings offer valuable insights for understanding caloric restriction and the tirzepatide-treated group, as well as a perspective on the clinical usefulness of proteomic aging clocks. 

Predictive plasma proteomics from the plasma professionals 

Have you ever donated plasma through a Grifols affiliate? [The author has]. If so, you may have contributed to the groundbreaking science behind Alkahest, a therapeutics company named after the mythical “universal solvent” sought by alchemists that analyzes data from millions of plasma donations to identify targets and diagnostic markers for disease. It’s no surprise that the “plasma experts” are using NULISA as part of their biomarker discovery efforts, starting with Parkinson’s disease (PD).  

SVP of Informatics Scott Lohr encourages researchers to “embrace the mess” and the complexity of plasma donation: people donate plasma for many reasons, but often they are repeat donors. Alkahest built the Chronos platform from a donation cohort to address critical gaps in PD, including biomarkers, therapeutic targets, and a better understanding of disease heterogeneity. The resulting “protein trajectories” offer opportunities to “look back in time,” akin to the James Webb Space Telescope looking billions of light-years in the past, to identify inflection points in PD progression. These protein biomarkers can be used to calculate risk scores for developing PD. Be on the lookout for a monumental publication in 2026. 

Wave of the future 

We are entering a “wave” of longevity and preventative science that is building in drug development and the wellness industry. Dr. Lasky-Su says, “The science is real” when it comes to preventive medicine. Unfortunately, there are still bad actors who often take an overly optimistic approach to the results. It’s up to us to better understand how the powerful biomarker tools inform, use them responsibly, and realistically navigate regulatory and implementation frameworks.   

Proteomics plays a crucial role in achieving the clinically meaningful goals of preventive and personalized medicine. According to Dr. Isaacson, “proteomics gives us the clarity—the right person, right dose, right time—to understand the heterogeneity of the people with a disease.” High-precision tools like NULISA are already providing the necessary data to make this possible. An important next step is to convince regulators and payers that changes in protein biomarkers signify genuine health improvements.