NPTX2 Protein Can Detect Cognitive Decline 7 Years Before Alzheimer’s Signs


Alzheimer’s disease, an escalating global health concern, necessitates early detection for effective intervention. Recent breakthroughs in Alzheimer’s research have spotlighted the potential of the protein NPTX2 as a key player in predicting the onset of cognitive decline, offering new avenues for early diagnosis and potential treatments.

Two comprehensive studies, both published in the Annals of Neurology, have illuminated the critical role of NPTX2 in identifying mild cognitive impairment (MCI) – an early stage of Alzheimer’s – years before symptoms become evident.

The Role of NPTX2 in Cognitive Decline

The first study, led by Dr Anja Soldan at Johns Hopkins University, explored the intricate link between NPTX2 levels and cognitive decline. The research involved tracking the cognitive status of over 250 initially mentally healthy individuals over an average span of 16 years. Among these participants, 77 eventually developed MCI or dementia.

The study’s revelation was striking: individuals with lower NPTX2 levels exhibited an earlier emergence of MCI symptoms. This correlation persisted for those progressing to MCI within seven years or beyond. Crucially, even when established Alzheimer’s biomarkers were accounted for, NPTX2 levels remained a potent predictor of cognitive impairment.

These findings underscore the potential of NPTX2 as a pivotal contributor to cognitive problems and suggest its significance as a robust marker for detecting early Alzheimer’s. The study’s authors emphasized the prospect of NPTX2 as a therapeutic target and called for further investigations to unravel its intricacies and variations across diverse populations.

How Can It Predict Alzheimer Early

In a parallel endeavor, the second study, also led by Dr Anja Soldan and published in the Annals of Neurology, reinforced NPTX2’s role as an early harbinger of cognitive decline. This research focused on NPTX2 levels alongside established Alzheimer’s biomarkers in cerebrospinal fluid samples collected from 269 cognitively normal adults.

The study found that lower baseline NPTX2 levels corresponded to an accelerated onset of MCI symptoms within and beyond seven years of the study’s commencement. Even after adjusting for other biomarkers and genetic risk factors, the association between NPTX2 and symptom onset persisted. The study also unveiled a connection between higher tau biomarkers and steeper NPTX2 declines, hinting at a link between tau pathology and NPTX2 levels.

NPTX2’s potential as a therapeutic target for Alzheimer’s and related neurodegenerative disorders was highlighted, with ongoing efforts to create a sensitive blood test to measure NPTX2 levels. Such a test could revolutionize early detection and risk assessment by providing a minimally invasive approach.

The Future Implications and Trajectory

Collectively, these studies elevate NPTX2 to a crucial biomarker for predicting the onset of cognitive decline, particularly in the context of MCI and Alzheimer’s disease. The connection between reduced NPTX2 levels and earlier symptom manifestation underscores the pivotal role of synaptic health in preserving cognitive function.

However, the studies acknowledge limitations related to participant demographics and the necessity for further research to comprehend NPTX2’s role fully. The studies together unveil a promising trajectory for research, with avenues to explore NPTX2’s interplay with brain structure, genetic and lifestyle influences, and broader applicability to various neurodegenerative conditions.


In the relentless pursuit of early Alzheimer’s detection and potential treatments, NPTX2’s emergence as a pioneering biomarker infuses new optimism. As research continues to unfold, NPTX2’s impact on the landscape of neurodegenerative disorders holds the promise of transformative advancements that could reshape how we approach and address cognitive decline and Alzheimer’s disease.


Anja Soldan, Sungtaek Oh, Taekyung Ryu, Corinne Pettigrew, Yuxin Zhu, Abhay Moghekar, Mei‐Fang Xiao, Gregory M. Pontone, Marilyn Albert, Chan‐Hyun Na, Paul Worley. NPTX2 in Cerebrospinal Fluid Predicts the Progression From Normal Cognition to Mild Cognitive Impairment. Annals of Neurology, 2023; DOI: 10.1002/ana.26725

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