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2023-08-02| R&D

Scientists Have Identified 32 Proteins Associated with Dementia Risk: A Promising Step Towards Early Detection and Potential Treatments

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Dementia is a growing global health concern, affecting millions of individuals and their families. As researchers strive to unravel the complexities of this devastating condition, two groundbreaking studies have shed light on significant biological pathways and potential therapeutic targets associated with dementia risk. Led by Daniela Neuhofer and Keenan Walker, these studies utilized distinct approaches to identify 32 proteins linked to dementia risk, providing unprecedented clues for predicting Alzheimer’s disease and related forms of dementia.

Related articles: FDA Granted Eisai and Biogen’s New Alzheimer’s Drug a Traditional Approval, Making Medicare Coverage Possible

Studying Dementia Risk and Its Progression in Midlife 

The research teams of Daniela Neuhofer and Keenan Walker embarked on a journey to explore dementia risk through midlife proteomic signatures. They examined the blood plasma proteins of 10,981 middle-aged adults, analyzing 4,877 proteins. Their findings pointed towards four overlapping biological processes significantly associated with dementia risk: proteostasis, immunity, synaptic function, and extracellular matrix organization. The significance of these biological changes is striking since they were detected outside the brain during middle adulthood, long before dementia symptoms became apparent.

The studies provided intriguing insights into the timeline of dementia development. Neuhofer’s team identified dysregulated immune and proteostasis/autophagy pathways around two decades before the onset of dementia. Additionally, abnormal coagulation and complement signaling appeared around 10 years before the disease emerged. On the other hand, Walker’s research emphasized the importance of certain proteins related to immune system function and protein regulation, appearing 20 years before dementia onset. Contrarily, proteins involved in the coagulation system and complement signaling showed signs of dysregulation in later stages of the disease.

Promising Therapeutic Targets and Alzheimer’s Prediction

The discovery of these 32 proteins opens exciting possibilities for future research. They hold the potential to serve as therapeutic targets, paving the way for interventions that could delay or prevent dementia onset. Additionally, these proteins present the opportunity to develop predictive tools for identifying individuals at higher risk of developing Alzheimer’s disease. Early detection could lead to personalized treatments and lifestyle modifications to reduce dementia risk.

Proteins Implicated in Dementia Risk

Among the identified proteins, several stood out for their potential roles in dementia risk. Proteostasis proteins, including DNJB9, DNAJB12, GABARAPL1, and HSPA1B, were elevated in participants who later developed dementia. These proteins play crucial roles in protein quality control and stress response and are associated with brain amyloid, p-tau, and neuroinflammation markers.

The immune system also played a central role, with proteins like GDF15 and SERPINA3 strongly associated with dementia risk. GDF15, an immuno-metabolic stress response protein, demonstrated the strongest association with 25-year dementia risk and was associated with midlife cognitive decline and neuroinflammation. SERPINA3, an innate immune protein, showed a positive association with dementia risk and AD but Mendelian randomization suggested it may be protective against AD.

Other proteins implicated in dementia risk include synaptic proteins like CBLN4 and GRID2, which also showed a strong positive association with amyloid status, and ECM/proteolysis proteins like MMP12 and MMP19, which were associated with dementia risk through vascular or immune pathways.

A Ray of Hope in the Battle Against Dementia

The groundbreaking studies led by Neuhofer and Walker provide invaluable insights into the biological processes associated with dementia risk, offering hope for early detection and potential therapeutic interventions. As the world grapples with the rising burden of dementia, these findings represent a significant step forward in the fight against Alzheimer’s disease and related forms of dementia.

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