Dementia: New Blood Test Identifies Risk Before Symptoms Appear

Researchers have studied blood biomarkers to predict dementia with Lewy bodies (DLB), a neurodegenerative disease. They analyzed samples from 158 people with a sleep disorder linked to diseases such as DLB and Parkinson's. They found that low levels of the protein Aβ42 and high levels of pTau181 in the blood were associated with the development of DLB. These findings suggest that blood tests could help identify early on those at higher risk of developing the condition.

A biomarker is any substance or biological characteristic that can be measured in the body and used to indicate a normal process, a disease, or the response to treatment. They can be found in blood, urine, saliva, cerebrospinal fluid, or even in imaging tests, such as MRI.

In neurodegenerative diseases such as Alzheimer's disease and dementia with Lewy bodies (DLB), biomarkers in the blood or cerebrospinal fluid can indicate the presence of abnormal proteins (such as amyloid-β and pTau181), helping in early diagnosis and monitoring of disease progression.

Blood biomarkers for Alzheimer's disease (AD) have been widely studied as possible indicators of neurodegeneration. However, Alzheimer's disease pathology can also be present in other neurodegenerative diseases, such as dementia with Lewy bodies (DLB).

Given that idiopathic/isolated REM sleep behavior disorder (iRBD) is often an early stage of these neurodegenerative diseases, researchers hypothesized that Alzheimer's disease-associated biomarkers in the blood could predict the conversion of iRBD to dementia with Lewy bodies.

The aim of this study was to evaluate whether plasma biomarkers amyloid-β (Aβ) and pTau181 can predict the development of dementia with Lewy bodies in a cohort of patients with iRBD.

A longitudinal study was conducted with 158 individuals diagnosed with iRBD by polysomnography, recruited between 2004 and 2022 in Canada. All participants provided blood plasma samples and were followed prospectively over time.

The follow-up allowed us to assess which of these individuals developed a neurodegenerative syndrome, with a special focus on conversion to dementia with Lewy bodies.

Blood levels of the biomarkers Aβ40, Aβ42, and pTau181 were measured using the NeuroToolKit panel, a suite of tests designed to detect proteins associated with neurodegeneration.

The main objective of the analysis was to determine whether blood levels of these proteins, measured at baseline, were associated with the later development of dementia with Lewy bodies.

In addition, the researchers assessed whether there was a correlation between these biomarkers and participants’ performance on baseline cognitive tests.

After excluding some participants, the final analysis included 142 individuals, 77% of whom were men, with a mean age of 67.6 years. During the follow-up period (an average of 2.9 years after blood samples were collected), 32 individuals developed a neurodegenerative syndrome.

Of these, 18 were diagnosed with dementia with Lewy bodies, 13 with Parkinson’s disease, and 1 with multiple system atrophy.

The results showed that individuals who developed any of these diseases had, already at the beginning of the study, a lower ratio between Aβ42 and Aβ40 in plasma and higher levels of pTau181.

When the analysis was focused specifically on individuals who developed dementia with Lewy bodies, the differences were even more evident. The Aβ42/40 ratio was even lower in these patients, and pTau181 levels were significantly higher.

In addition, cross-sectional analyses indicated that plasma pTau181 levels were associated with deficits in cognitive tests, suggesting that this biomarker may be related to cognitive impairment even before conversion to dementia with Lewy bodies.

However, the Aβ42/40 ratio did not demonstrate the same correlation with cognitive tests. These findings suggest that blood biomarkers Aβ42/40 and pTau181 may be useful in predicting the conversion of iRBD to dementia with Lewy bodies.

Early identification of these patients may allow for more effective interventions and improve clinical monitoring, enabling a more targeted approach to slow or manage disease progression.

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Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder

Aline Delva, Amélie Pelletier, Emma Somerville, Jacques Montplaisir, Jean-François Gagnon, Gwendlyn Kollmorgen, Tony Kam-Thong, Thomas Kustermann, Venissa Machado, Ziv Gan-Or and Ronald B Postuma

Brain. awaf003, 6 January 2025

DOI: 10.1093/brain/awaf003

Abstract: 

Blood-based biomarkers for Alzheimer’s disease (AD) pathology have been intensively investigated as markers for AD-related neurodegeneration. Comorbid AD pathology is common in dementia with Lewy bodies (DLB). Accordingly, we hypothesized that plasma biomarkers associated with AD pathology might be useful to predict DLB in a cohort of idiopathic/isolated REM sleep behavior disorder (iRBD), an incipient synucleinopathy. The aim of this study was to determine whether plasma amyloid-β and pTau181 biomarkers can predict DLB. This longitudinal single-center (Canada) cohort study included 158 polysomnography-confirmed iRBD individuals between September 2004 and October 2022, each providing blood plasma samples, who were then offered prospective follow-up. Plasma Aβ40, Aβ42 and pTau181 levels were measured using NeuroToolKit, a prototype assays panel of neurodegeneration (Roche Diagnostics International Ltd). The primary outcome was the association between plasma biomarkers at baseline and eventual development of DLB. Correlations between plasma markers and baseline cognitive tests were assessed. A total of 142 iRBD participants (109 men [77%], mean ± SD age, 67.6 ± 8.0 years) were included in the final analysis. On prospective follow-up (2.9 ± 2.1 years after sampling), 32 individuals phenoconverted to a defined neurodegenerative syndrome (18 DLB, 13 PD, 1 MSA). The combined phenoconvertor group had lower baseline plasma Aβ42/40 ratio compared to non-phenoconvertors (mean ± SD, 0.103 ± 0.010 vs. 0.114 ± 0.012, p < 0.001), and higher pTau181 levels (0.993 ± 0.354 vs. 0.784 ± 0.266pg/ml, p = 0.008). When divided by phenoconversion subtype, significant differences were seen selectively in DLB-convertors (Aβ42/40 = 0.101 ± 0.010, difference -0.011, 95% CI [-0.016; -0.005], p < 0.001; pTau181 = 1.144 ± 0.326 pg/ml, difference 0.282 pg/ml, 95% CI [0.146; 0.418], p < 0.001). Cross-sectional analysis showed that plasma pTau181 (but not Aβ42/40) correlated with cognitive tests across various domains. Our results indicate that plasma Aβ42/40 ratio and pTau181 can predict conversion to DLB in iRBD.