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Core Alzheimer pathologies are reflected in blood markers

Studies that combine several blood markers are promising in the differential diagnosis of dementia. And -- even ten years in advance of CSF/PET positivity -- a combination of plasma markers can detect the presence of amyloid pathology.

Blood-based biomarkers now have the potential for implementation in clinical practice for the screening, diagnosis, prognosis and monitoring of people with Alzheimer’s disease (AD). This take home message was bold. Concluding her plenary address at AAIC2020, Charlotte Teunissen (Amsterdam University Medical Center, The Netherlands) based her confidence on recent data showing the value of combining blood markers that reflect the different pathological processes contributing to AD.

Combining markers gives a more complete picture of AD pathology and should increase accuracy

 

Combinations give greater insight into AD complexity

Studies have involved several clinical cohorts in whom researchers have measured amyloid-β (Aβ) 42 and 40 isoforms, tau phosphorylated at amino acid 181 or 217, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).

Perhaps most striking was evidence from the Netherlands Twin Register-Biobank study – presented by Anouk den Braber – that plasma amyloid-β1-42/1-40 and GFAP levels in cognitively unimpaired individuals predicted amyloid positivity on CSF/PET measures ten years later.

The combination of baseline amyloid-β1-42/1-40 and GFAP had an AUC of 0.89, a sensitivity of 0.75 and a specificity of 0.96. For comparison, the corresponding figures for the amyloid-β1-42/1-40 marker on its own were 0.69, 0.42 and 0.98.

Also at AAIC2020,

 

  • Data from Inge Verberk and colleagues showed that serum GFAP and NfL can predict conversion to dementia over 4-8 years in people with subjective cognitive decline
  • Professor Teunissen presented evidence that plasma levels of GFAP and NfL relate to global cognition, memory, language, attention and executive function
  • In a multiplex analysis including age and ApoE status, amyloid-β1-42/1-40 , GFAP and NfL predicted PET positivity with an AUC of 88%, sensitivity of 82% and specificity of 86%.

 

Blood will tell

These findings build on earlier data demonstrating, for example, that the age, sex and ApoE-adjusted plasma amyloid-β 42/40 ratio predicts conversion to mild cognitive impairment or dementia over five years in people with subjective cognitive decline and abnormal baseline amyloid.1

Elisabeth Thijssen and colleagues have also recently published evidence that plasma pTau-181 identifies amyloid and tau-PET positivity.2 Tau181 concentrations were 3.5 times higher in AD than in controls and distinguished AD from clinically diagnosed and autopsy-confirmed frontotemporal lobar degeneration.

Such blood-based assays, which are relatively non-invasive and can be repeated, bring us closer to the screening tools we need to aid the development of disease-modifying drugs in people at risk of AD, Charlotte Teunissen believes. They will also enable the closer monitoring of people who already have the condition.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References

1. Verberk I et al. Ann Neurol 2018;84:656–666

2. Thijssen E et al. Nature Medicine 2020;26, 387–97

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