This can now be detected by a simple blood test.  

The Scientific American this month guides us to the fact that there now exists a laboratory test for Alzheimer’s disease. 

Memory loss is a common feature to all of us and can be of no particular consequence, especially during this pandemic when most people are mildly depressed or fatigued.  

In the past, Alzheimer’s could only be diagnosed at autopsy.  Then brain imaging and spinal taps made it possible to spot the disease in patients before initial symptoms appeared, but these are invasive tests, which are expensive and have in the past been limited to research settings.  A blood test developed by C2N Diagnostics in St Louis has been awarded the CE mark as a diagnostic medical test in the EU.

The C2N test called PrecivityAD, uses an analytic technique known as mass spectrometry to detect specific types of beta-amyloid, a protein fragment that is a pathological hallmark of disease.  Beta-amyloid proteins accumulate and form plaques visible on brain scans two decades before a patient notices memory problems.  As plaques build up in the brain, levels of beta-amyloid decline in the surrounding fluid.  Such changes can be measured in spinal fluid samples – and now in blood, where beta-amyloid concentrations are significantly lower.  

PrecivityAD is the first blood test for Alzheimer’s to be cleared for widespread use and one of a new generation of such assays that could enable early detection of the leading neurodegenerative disease – perhaps decades before the onset of first symptoms.  

It is suitable for 60 to 91 year olds with early signs of cognitive impairment.  Blood samples are analysed at C2N’s lab and results should be back within two weeks.  Results give a probability score, which reflects the likelihood of an amyloid positive brain scan – a proprietary algorithm that incorporates the person’s age with measurements of beta-amyloid and a protein called apolipoprotein E that is known to influence Alzheimer’s disease risk.  

This test is not a standalone tool, but the results are meant to enhance the accuracy of a clinical diagnosis by distinguishing Alzheimer’s dementia from memory loss caused by other conditions. 

From a preventative standpoint, blood tests can help to identify those at risk.  It will help to screen potential participants for experimental drugs.  In some past trials of beta-amyloid reducing treatments, 15-30% of patients who met clinical criteria for Alzheimer’s turned out not to have brain amyloid.  Screening would help to half the number of PET scans required to enrol volunteers in Alzheimer’s drug trials.  

However, looking for beta-amyloid is not the only option and some researchers believe other disease markers – for example, certain forms of the protein tau could prove more promising when incorporated into blood tests for Alzheimer’s.  Amyloid levels start to drop very early in the disease process and then reach a plateau, whereas tau markers go up later and continue to rise.  This observation suggests amyloid tests could work better for early detection while tau levels are more meaningful at later stages of the disease, when someone is at the verge of decline or already symptomatic.  

Oskar Hansson, a neurologist at Lund University in Sweden published with Thijssen, a researcher studying blood biomarkers at Amsterdam University, separate studies, which showed that tau blood tests could distinguish Alzheimer’s from other neurodegenerative diseases nearly as well as CSF measurements and PET scans. 

Quanterix, a company in Billerica Massachusetts has developed an immunoassay that detects amyloid and tau in conjunction with other neurological markers and inflammatory proteins.  However, these tests are not available outside research settings.  

It has to be remembered though that the accuracy of these assays can be influenced by other conditions.  Chronic kidney disease can affect the clearance of proteins and individuals with a high body mass index tend to have higher blood volume which could reduce protein levels. 

The London General Practice has developed a healthy mind pathway and applauds this research and biomarker tools which can aid in the diagnosis of Alzheimer’s.

Dr Paul Ettlinger
BM, DRCOG, FRCGP, FRIPH, DOccMed

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