The Angel and the Assassin by Donna Jackson Nakazawa

Author:Donna Jackson Nakazawa
Language: eng
Format: epub
Publisher: Random House Publishing Group
Published: 2020-01-20T16:00:00+00:00

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Let’s imagine all of this in a potential real-life scenario.

Imagine a woman in midlife, like Katie, whose grandmother died of early-onset Alzheimer’s. Now imagine that she has tested positive for several genetic mutations, such as the TREM2 and ApoE4 gene mutations, which are known to increase an individual’s chance of developing early-onset Alzheimer’s. Just as a woman with a family history of breast cancer might go in for more regular mammogram screenings, Katie might go in for microglial PET scans every year. Let’s say she’s forty-five and her yearly microglial PET scan shows that a certain small area of her brain is lighting up, indicating that regulatory genes expressed in microglia are starting to change in an ominous way that’s been linked to Alzheimer’s. Synapses in a specific area of the hippocampus are going to go down.

Katie’s radiologist gives the report to her doctor, who then sends her for prophylactic gamma light flicker therapy. She will very likely also have Katie work with a behavioral therapist to adopt specific dietary and exercise programs that have also been shown to help create neurogenesis. Knowing too that less-active synapses are more likely to be tagged by complement and pruned away, Katie might learn a new language, start doing Sudoku, or take up knitting—or all three. She’ll probably work hard to avoid environmental toxins, pathogens, infections, and stressors, which have been shown to contribute to triggering overtaxed microglial immune cells to become hyperactive. By then, we may well have noninvasive interventions that also help the brain to better drain plaque debris out through the meningeal lymphatic vessels, and perhaps even successful microglial pharmaceutical interventions that work without doing harm.

Very likely some of these therapies will be used in winning combinations. For instance, the researchers in Australia who recently discovered, like Tsai, that delivering light waves can clear amyloid plaques in animal models also discovered, in 2017, that when they combined a biologic immunotherapy (one which delivers antibodies to help decrease immune-activated inflammation in the brain) with therapeutic ultrasound, it significantly enhanced the effect of the immunotherapy and the reduction of amyloid plaques and tangles.

In our future hypothetical, Katie doesn’t have to try all available interventions at once—she can try one or two at a time and continue to go in for regular microglial PET scans as she and her doctor monitor which therapies are working in her individual brain, given her genetic profile. Over the next year, they can put together a combined treatment plan, one that they can see is succeeding in real time—and one that will prevent the forest fire of Alzheimer’s from ever becoming fully kindled in Katie’s brain in the first place.

And one day, perhaps a decade from now, a teenager might be able to go in to her pediatrician’s office for a yearly blood test to screen for specific signatures that reveal microglia are shifting their activity—the same way we now screen preteens for cholesterol. If the test indicates microglial or synaptic changes that

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