Blood test detects early Alzheimer’s signs in people with memory concerns

Researchers have shown that a simple blood test for plasma P-TAU181 can mark subjective cognitive decline, an early but biologically clear stage in Alzheimer’s, years before traditional symptoms appear.

Study: Blood biomarkers confirm subjective cognitive decline (SCD) as a clear molecular and clinical stage in the NIA-AA framework of Alzheimer’s disease. Image Credit: Belight / Shutterstock

Published in a recent study in the magazine Molecular psychiatryA group of researchers evaluated or blood biomarkers subjective cognitive decline (SCD) can distinguish as a clear transition stage in the progression of Alzheimer’s disease (AD).

Background

What if a simple blood test can detect ad years before the symptoms appear? Ad starts long before memory loss and progresses quietly due to biological changes. The National Institute on Aging and Alzheimer’s Association (NIA-AA) defines six phases of AD, where phase 2 represents a subtle shift of normal cognition, often experienced as SCD. Although individuals can feel their memory slipping, standard tests generally do not reveal deficits. Identifying reliable molecular biomarkers for this phase can cause a revolution in early detection and intervention. However, it is important to note that, although promising, the current research suggests that these biomarkers are best used for prediction at group level instead of individual clinical diagnosis. Further research is needed to validate these biomarkers and their predictive power for clinical progression on an individual level.

About the study

Researchers used data from 457 participants in the longitudinal cognitive disorders and dementia study (Delcode), coordinated by the German Center for Neurodegenerative diseases. All participants were 60 years or older and categorized in clinical groups based on cognitive status and cerebrospinal liquid (CSF) biomarkers. Amyloid positivity was determined using the CSF-amyloid beta 42/40 (Aβ42/40) ratio, aligned with the NIA-AA criteria. This made classification possible in amyloid-positive cognitively unscathed (A+ CU), amyloid-positive subjective cognitive decline (A+ SCD) and amyloid-positive mild cognitive disorders (A+ MCI). Amyloid-negative groups were also included for comparison: A-CU, A-SCD and A-MCI.

Plasmamonsters were analyzed at levels of fosphorylated Tau at Threonine-181 (P181) and Neuroilament Light Chain (NFL), which represent Tau-Pathology and Neurodegeneration in the Amyloid-Tau-Neurodegeneratie (ATN) Framework. Cognitive performance was assessed annually with the help of the pre -clinical Alzheimer’s cognitive composite (PACC5), and the hippocampal volume was followed through imaging of magnetic resonance. Longitudinal data analysis used linear models with mixed effects to evaluate biomarker trajectories and their relationship with cognitive decline and structural brain changes. Kaplan-Meier survival analysis and COX registration models were used to assess whether Baseline Biomarker levels predicted progression from A+ SCD to A+ MCI, and from A+ MCi to AD dementia. All analyzes were adapted for age, gender and education. The study specifically noted that all participants gave informed permission and that the research was conducted in accordance with ethical standards.

Study results

At the start, plasma P181 -levels were significantly increased in A+ SCD compared to A+ CU. These levels in A+ SCD also increased faster over time and resemble patterns that were seen in A+ MCI, which suggests a clear biological profile in stage 2 of AD. NFL levels, on the other hand, were higher in A+ SCD compared to A – SCD, but differences between A+ SCD and A+ CU were not statistically significant. NFL levels, however, increased steadily on A+ CU, A+ SCD and A+ MCI, which reflect progressive axonal degeneration along the continuum.

Cognitive decline, measured with the help of the PACC5 composite, was considerably more pronounced in the course of time at A+ SCD individuals. While A+ CU individuals showed stable performance, A+ SCD participants demonstrated a negative cognitive process that further deteriorated in A+ MCI. High basic plasma P181 levels were predictive for faster cognitive decline in A+ SCD, but not in A+ CU, and this relationship continued in the MCI phase. NFL levels, however, only predicted cognitive decline in the MCI stage and not before.

In addition, higher basic line P181 levels in A+ SCD predicted the transition to MCI during a three-year follow-up. Almost 30% of the A+ SCD individuals converted into MCI, compared to 17% of the A -SCD participants. This risk was almost three times greater for people with increased P181 levels. Likewise, higher P181 levels at the MCI also predicted the progression to ad -dementia at the start. These findings support the potential of P181 as a stratification biomarker for early in the course of the disease of a high risk. However, the authors warn that these findings are currently the most robust at group level, and further validation is required before such predictions can be reliably applied to individual patients in a clinical setting.

Neuroimaging findings partially confirmed biomarker data. At the start, A+ SCD participants had reduced the hippocampal volume compared to cognitively unjusted individuals. However, significant associations between hippocampal atrophy and plasma biomarkers were only clear in A+ MCI, which suggests that structural changes are left behind in molecular changes in early diseases. The study notes that the shorter follow-up period may have limited the ability to detect robust associations between MRI findings and blood biomarkers in earlier stages.

Together these results A+ SCD validate as an organic and clinically clear stage within the AD continuum. Plasma P181 levels offer a valuable tool for identifying persons with a high risk of future cognitive decline and clinical progression, while NFL offers extra support for underlying neurodegeneration in stage 2. The study emphasizes the potential role of plasma P181 in the most of the dating of future vocal varying.

Conclusions

This study confirms that SCD represents a separate and detectable transition phase (stage 2) within the NIA-AA AD continuum for A+ individuals. Plasma Fosphorylored Tau at P181 comes to the fore as a reliable blood biomarker, which is able to identify it with an increased risk of cognitive decline and clinical conversion to MCI or AD dementia. Although NFL supports proof of neurodegeneration, the individual process of P181 emphasizes its central role in early AD pathology. It is important that the authors emphasize that the current predictions of biomarkers must be interpreted at group level and that further research is needed for their application in individual diagnosis and care. These findings support blood-based biomarkers for early AD diagnostics and intervention.