Her autopsy report: sadness, anger and meaning

Over one hundred years ago,1907, Dr. Alois Alzheimer published his now famous brain autopsy of a 51 year old woman named Auguste, who had memory and behavioral problems before dying. Syphilis was more common then; “The Great Imitator” had similar symptoms. Using a microscope from that era, he could identify changes in brain tissue that were not syphilitic, and are now called amyloid plaques and tau neurofibrillary tangles.  A contemporary, Dr. Oskar Fischer made similar observations the same year. The condition came to be called Alzheimer’s Disease (AD).

In most of the last century, one learned that AD could only be diagnosed with certainty after death, with characteristic findings on brain autopsy.  Over the years, diagnostic labels could be applied on clinical grounds, with improving conventional brain imaging along with a battery of neuropsychological tests.  As the condition became more recognized, AD started showing up as a frequent cause of death, recently the sixth leading cause of US death. 

From my outsider’s view, the pathology findings led to the characterization of the proteins involved in plaques and tangles, namely beta-amyloid and tau.  And that led to theories about the roles of these proteins in the disease, abnormal when found, but seemingly derived from the human brain cells themselves.  Medical thinking is fairly linear so that anti-amyloid and anti-tau probes and therapies were developed when they could be.

So what does this history have to do with the donation of my late wife’s brain to an Alzheimer’s Disease Research lab?  And what did it mean to me to get her report?  

The decision to do the donation did not come easily, and but we could share the burden with a family discussion.  It was a hard and emotional decision, but we came to a consensus the year before her death.  Her pattern of deterioration at home seemed to fit Reisberg’s FAST scale for dwindling abilities, but not its timeline.

The consenting happened online; it’s not a spur of the moment process. It’s considered a donation, with their own work and expertise handled by their own grants and funding.  They said it would take quite a while before a report would be ready, but they would notify us and share it if we were interested.  We could have someone go over the findings with us.

When I opened the report, I have to confess I felt a breath-stealing, constricting grip of sadness. It was all there, written in technical language but understandable to me, verifying the severity of her condition. I whipped through it once and had to put it down. 

I knew it was her, but it was not her. How could it be her?

I hesitated, but picked it up after some deep breathing, to read details more closely. There was evidence of a severe burden, amyloid and tau, that met AD (CERAD) criteria, and a factor the lab now tests for, TDP-43. That’s another proteinopathy, found with numerous clinical correlations, including ALS and a pattern of dementia that starts in 80-somethings, with the acronym LATE.

I knew that no pathologist, no clinician, could answer our biggest question: WHY HER? She was otherwise healthy, with no vices, and no “risk factors,” she was sociable, a loving parent, generally happy, productive and accomplished.  Could they find a clue?

Although realistic enough to have no expectations of answers, other questions arose. Was there a whisper of an etiology, or a mechanistic HOW her condition happened? There were pertinent negatives: no stroke or significant vascular disease, no signs of previous head trauma or sequelae of infection, etc.

We had the privilege of having a family conference with both the pathologist and a master clinician who helped us understand the perspective of her findings.  We were internally providing our own contexts, of her individuality, her specialness that we knew and loved deeply.  Afterall, each case coming to this kind of examination is special in a way that a microscope couldn’t reveal.

We learned that there were nuances.  On the other hand, since there is no specific pattern that fits young-onset disease pathology (she was 57 when symptoms started), her findings may be her own, and unique. The distribution of findings were consistent with her clinical course. There was no pattern that would lead to a recommendation for genetic testing of family members.  

We learned that her findings would be de-identified and shared with other researchers, and that some tissue was saved for future technologies and research as they arise.  We provided an extensive narrative clinical and family history, including some of the symptoms she had during home care.

The most emotionally shocking thing to me was the demonstration of atrophy.  Shrinkage is too glib a description for me now, and I think of it as a mean metaphor used in aging.  I had been shocked when I glimpsed her emergency CT years ago that I thought showed atrophy, so I expected it and don’t know why it hit so hard. Except for microscopic neuronal loss, the tissue wasn’t revealing a trail of pathophysiology.

By the next morning, I woke up a bit angry.  How could her own neurocellular machinery, which worked brilliantly for so long, get perverted so that her brain was riddled (deliberate double entendre) with abnormal proteins?  I wasn’t angry at her, or her brain, or the report, but it was the same feeling I had when encountering brain tumors in infants, the feeling of innocence done down and dirty. And then I realized she wouldn’t have wasted energy on anger.  She had already accepted it and moved on.

So I’m not saying our family is more altruistic or far-sighted than others in providing this donation; afterall, we got a lot out of it on a personal level. And we got to remember her again and share anecdotes. But my wife had set the example for us, as a caring family doctor, with lots of love and friends in her life, active in social justice, and she also knew intimately how hard it is to learn medical things.

But the bigger picture for us: we can’t know if this report will really contribute to current research or provide a line to develop a new therapy, or provide that Eureka insight for a researcher yet to be born, or a create an idea for real prevention.  It’s not closure. There are more questions. But even Artificial Intelligence needs reliable data to scan in for its algorithms. And we are grateful for the individuals with whom we met, and the cadres of researchers they represent. And all that, with the hope that there can be an impact, makes this meaningful to me.