Progress on blood tests for Alzheimer's disease

Back in January, we discussed some promising advances in Alzheimer's disease research, noting that we could soon get some very good news on several blood tests for early detection of the disease.  Most of our hopes had been riding on tests to detect beta amyloid in the blood, but there was also some hope for a test for blood serum tau protein.

Recall that both the malformed protein beta amyloid and a certain variety of tau protein in the brain are recognized biomarkers for Alzheimer's disease.  These can be detected using a PET scan, but this is usually done after symptoms have developed.  Since the disease starts a decade or two before the first symptoms appear, the hope is that very sensitive tests could detect the buildup of these factors early.  And we have been hoping that some apparently ineffective drug interventions might actually work if we could start people before they showed symptoms.

The 2019 Alzheimer's Association Facts and Figures Report described our understanding of how the disease progresses in the brain.  It noted that Amyloid accumulates in the cerbrospinal fluid until the first cognitive symptoms appear.  At that point, the pathologic tau suddenly bursts out of the cells and spreads throughout the brain, although some had likely been getting out all along.  The expulsion of the tau protein coincides with the appearance of the "tangles" that Alois Alzheimer noted in a brain autopsy in 1906.

The focus of the search for a blood test had focused on finding trace amounts of amyloid, but that can be tricky.  At first the amyloid builds up in the brain and blood, but then it begins to agglomerate on the brain cells.  So at that point, the concentration of amyloid in blood and cerebrospinal fluid begins to go down instead of up.  That makes interpreting the results a little harder.

So there is also attention on the protein p-Tau181.  The hope is that this will be a more reliable biomarker, and a couple of recent studies support this hope.  At the recent Advances in Alzheimer's and Parkinson's Therapies meeting, participants discussed some recent research showing that very small concentrations of tau protein could be detected in the blood, and the concentrations could be specifically correlated with the advent of Alzheimer's disease.  This was very promising.

The meeting is normally held in Vienna, Austria, but it was conducted online this year due to the pandemic.

Why do we want to know if someone has Alzheimer's disease before it manifests itself in cognitive symptoms?  Most Baby Boomers don't want to know.  They likely saw a parent or other loved one live through it, maybe die from it, and they believe that there's nothing that can be done about it.  So what good would it be to know?  (They should read Beating the Dementia Monster.)

Certainly, the long-term care insurance companies would like to know.  They will want to screen out applicants that will likely develop Alzheimer's dementia in the coming years.

The real benefit is to the researchers, at least for now.  It's believed that acting early, well before symptoms of cognitive decline appear, will be much more powerful than waiting until someone has already developed MCI or dementia.  So it's important to find preclinical research subjects.  In the past, researchers have used preclinical test subjects with the younger-onset variety of the disease, because they can be confidently identified through genetic testing.  But a reliable blood test for preclinical test subjects with the older onset variety will break down some of the biggest hindrances to the effectiveness of Alzheimer's research.