It’s in the blood – identification of plasma biomarkers brings hope for screening and early detection of Alzheimer’s disease

In the opening keynote lecture at the 11^th Clinical Trials in Alzheimer’s Disease (CTAD) Congress, Professor Randall Bateman, Washington University School of Medicine, St Louis, USA, shared his enthusiasm for blood biomarkers which, he said, offer huge potential for the early identification of Alzheimer’s disease even before symptoms become apparent.

We know that pathological changes – the appearance of amyloid-β (Aβ) plaques in the brain – can occur some 20 to 30 years before symptoms begin to show, he explained, and the early detection of these biological changes offers a real opportunity to intervene early and prevent the development or worsening of Alzheimer’s disease.

The blood β-amyloid test can detect Aβ plaques in individuals before symptom onset

Professor Bateman and co-workers have identified the blood β-amyloid test which can be used to detect Aβ plaques in individuals before symptom onset. The blood β-amyloid test is validated in longitudinal studies, and fragment Aβ42/40 ratios measured in plasma correlate well with the current gold-standard measures of amyloid positron emission tomography (PET) scan and the invasive β-amyloid in cerebrospinal fluid (CSF) test for detection of Aβ plaques in the brain.¹

Population screening for Alzheimer’s disease is a step closer

In future, Professor Bateman said, the blood β-amyloid test may be used to screen millions of people in the general public to identify who is at risk for Alzheimer’s disease. Once effective treatments are discovered, these people will be able to start treatment even before memory loss and brain damage begins. Furthermore, the blood β-amyloid test can be used to better identify patients for clinical trials, which will speed discovery of Alzheimer’s disease prevention and treatment.

The blood β-amyloid test can be used to better identify patients suitable for clinical trials

The use of a single blood test screen for Alzheimer’s disease could reduce the number of PET scans needed by around 50%. It will save on screening time, and increase the number of screening sites, such that implementation in the general population becomes much more feasible.

The blood β-amyloid test offers potential savings in number of PET scans needed and screening time

A breakthrough in blood-based biomarkers

The search for a plasma-based biomarker of amyloid plaques has been a challenge for the past two decades, and yielded only mixed results with low accuracy until 2017.² Aβ is actively transported across the blood brain barrier via the CSF into the bloodstream in the normal brain.³ However, altered clearance of fragment Aβ42 kinetics associated with Alzheimer’s Aβ is found in the CSF surrounding the brain.⁴ Professor Ramsay et al. demonstrated that fragments of Aβ detected in the plasma show the same Alzheimer’s Aβ plaque pattern as that detected in the CSF (Aβ42/40 ratio).¹ Furthermore, in studies following patients for up to 7 years, plasma and CSF Aβ42/40 identifies and predicts conversion to positive amyloid PET status with high sensitivity (0.88) (Ramsay, unpublished).

Shining a light on future progression

One of the most exciting recent developments in blood biomarkers is the identification of plasma neurofilament light (NFL), Professor Bateman explained. Plasma NFL is increased in people with Alzheimer’s disease and those with mild cognitive impairment (MCI). Not only can plasma NFL be used to identify patients, but also plasma NFL is associated with the future rate of cognitive decline, and is a biomarker for neurodegeneration.⁵ Thus, plasma NFL could be the prognostic biomarker of the future, able to predict both clinical and cognitive performance.⁶

Plasma NFL could be a prognostic biomarker of future clinical and cognitive performance

Ongoing research will expand the panel of blood biomarkers and help to advance early detection and treatment of Alzheimer’s disease, resulting in better outcomes for patients, concluded Professor Bateman.