S2E8. Breaking News: It’s Not The Plaques & Tangles!

Do you remember the dreaded 500-word essay in high school? Coming up with what I wanted to write about was the hardest part for me, along with writing the first sentence. After that, it was pretty much clear sailing.

Writing this blog reminds me of those days. Each week, the hard part is coming up with a concept and then deciding how I want to begin. Usually, I have an idea in my head by Monday, but this week was different. By Monday, I had nothing. Tuesday was no better. Wednesday morning: bupkis! 

I was in trouble at that point because I usually finish writing by Wednesday night and send my draft to Sally for proofing.

Luckily for me, I downloaded a book several weeks ago that I thought might be interesting to explore down the road: How Not To Study A Disease: The Story Of Alzheimer’s by neurobiologist Karl Herrup. I decided that ‘down the road’ was now and began to read furiously to meet my deadline.

Herrup’s theme is that we’ve wasted many years and billions of dollars in the search for an Alzheimer’s cure because we didn’t heed what the research told us and instead became locked into one particular theory of the cause of dementia. He argues that, over the past twenty years, due to a combination of greed, stubbornness and bad advice, both the government and pharmaceutical companies only explored the beta amyloid cascade hypothesis that plaques and tangles cause the symptoms of dementia and that removing them would cure it.

I admit that I frequently got lost during his deep dives into the microbiology of cell function and the chains of chemical reactions that create various important proteins. And I appreciate that he’s trying to explain the tension between the arcane worlds of basic and applied biological research and the politics and egos that contribute to it. Unfortunately, though, that story line didn’t really grab my interest. I was eager to get to the end where he promised to present his approach to what we should be studying going forward.

Herrup does do a good job, however, in making it clear that the research that has been conducted pretty conclusively rejects the beta amyloid cascade hypothesis as the primary cause of Alzheimer’s disease. To whit: about 30% of the elderly with more than a critical mass of plaques and tangles show no signs of dementia while about 15% without plaques and tangles are properly diagnosed with dementia. He also explains the valuable knowledge gained from animal studies that should have given us a heads-up that beta amyloid wasn’t at the heart of the problem.

So, if it’s not beta amyloid peptides and the dreaded plaques and tangles, then what is it?

Herrup places his understanding of the possible causes of Alzheimer’s inside our understanding of aging. He details a few of the normal aging processes that can lead to brain cell death and then explains how these processes might be the ones that run amok in Alzheimer’s.

He continues by building a model of the brain that incorporates all of the different types of cells in the brain, not just the neurons. It is the interactions between these different cells, he argues, that set the stage for the breakdowns that lead to cell impairment and death. Inflammation, loss of myelin sheath, beta amyloid accumulation, and insulin resistance are all addressed within the model, and he offers suggestions for lines of future research.

In this brief summary, I certainly have not done the model justice. It’s well-worth reading to see how he integrates so much disparate information into a cogent and cohesive theory.

It was truly awe-inspiring for me to learn about the complexity of cell functioning at the biochemical level and how the different types of cells support each other. It’s a marvel of bio-engineering that is absolutely mind-boggling, to say the least! 

It’s 12:21pm on Thursday afternoon. I just finished reading the book and writing this draft. Time to send it along to Sally…and in plenty of time to get it to you on Friday morning.

__________