News for Nerds -- New Insights from PET Scans

The science of using positron emission tomography (PET) scans to study how Alzheimer's disease progresses is advancing.  In my case, they used MRIs to produce images showing the progressive atrophy of my brain, but PET scans can show a lot more about what's actually going on in different cases.  My doctors would have wanted to do a PET scan, but it would not have led to any change in my treatment, and the cost couldn't be justified.  PET scans are more expensive than MRIs and would only yield interesting information of no practical value.  PET scans are, of course, used extensively in research on Alzheimer's disease.

In a PET scan, the subject is injected with a dye (tracer) containing atoms that radioactively emit positrons -- anti-matter electrons.  The anti-matter electrons quickly find regular electrons with which they undergo "annihilation."  (The physics teacher in me can't resist...)  This is where E=mc^2 comes in.  Both particles are converted to pure energy in the form of gamma rays following Albert Einstein's famous formula.

Instruments around the brain measure these gamma rays and can map where the dye is accumulating.  The tracer can be formulated to accumulate in amyloid plaques or in the tau tangles.  These are characteristic of Alzheimer's disease, although they could result from other causes at lower quantities.  An important way that PET scans are used is to see how and where glucose is being used in the brain.  Changes in how glucose is used in the brain may indicate Alzheimer's disease.

Each case of Alzheimer's disease unfolds a little differently, and PET scans can be used to examine how the brain is being affected in different cases.  For example, I believe that my most significant initial symptom was Benson's syndrome (or the visual syndrome) that affected how my brain processed visual information.  I began to notice this at about the same time I began having cognitive issues, but I'm not sure which was first.  Perhaps a PET scan at the time would have found more tau buildup in the occipital lobe of my brain where visual images are processed.

One of the findings of the Nun Study was that some women whose brains showed, during autopsy, significant damage along with the plaques and tangles characteristic of Alzheimer's disease nevertheless had normal cognitive function before they died.  I read one of the autopsy reports which noted the distribution of the plaques could have influenced how the disease was expressed.  (I did not see any effort to correlate lifestyle behaviors, such as physical exercise, with an apparent disparity between disease and cognition.)  So PET scans can be a valuable too in studying the different ways that Alzheimer's disease progresses.

What prompted me to write all of this was an article in this week's ALZForum, "Can PET Match Up Areas of Protein Deposit With Alzheimer’s Symptoms?"  The article reported on The Human Amyloid Imaging Conference, held in Miami January, 15-17.  The article was kind of dense, but it made some interesting points.

In my mind, one thing it reinforced was our understanding that beta amyloids build up slowly over the years until some sort of tipping point.  Suddenly, there's a virtual explosion of tau protein in the brain that corresponds with the first appearance of cognitive problems.  One study underscored an emerging understanding that initial buildup of beta amyloid may correspond with early indications of cognitive problems, but tangles appear to be implicated in the later stages of the disease.

One study discussed at the meeting analyzed the uptake of tracers indicating that more tau deposition occurred in the medial temporal lobes, the hippocampus, and the amygdala of people showing evidence of cognitive decline. The researchers said, “data suggest that tangle accumulation in these regions can precipitate cognitive decline.”

Recall from Beating the Dementia Monster that microtubules form a sort of skeleton for the cell, and these are given their strength by tau protein.  In Alzheimer's disease, an abnormal form of tau protein appears that fails to provide sufficient strength for the microtubules, and they collapse into a "tangle."  These tangles were first observed by Alois Alzheimer when, in 1906, he performed an autopsy on the brain of Auguste Deter.  (This was but a few months after Albert Einstein published his very famous series of papers, including one that gave us E=mc^2.)