In the winter of 1901, Auguste Deter stumbled through the door of Frankfurt’s Institution for the Mentally Ill and Epileptics—known among the locals as the Castle of the Insane. Auguste had no idea where she was or, really, who she was. A wife had lost her way.
Meanwhile, at the Castle, 37-year-old physician Dr. Alois Alzheimer also lost his wife, a plucky young woman who proposed to Alois, gave him three children, and left him an enormous fortune.
Auguste Deter never left the Castle. She died four years later, upon losing the last shred of her memory and self-awareness. Although senile dementia was a recognized condition at the time, the woman was in her early 50s, hardly senile.
In Auguste’s brain, Dr. Alzheimer found two abnormalities: deposits of an unknown substance scattered between neurons, and tiny fibers growing inside neurons. These findings, together with Auguste’s symptoms, led to the naming of a new disease: a pre-senile dementia, aka, Alzheimer’s Disease (AD). Incidentally, those are the initials of its first patient: Auguste Deter.
In the 1760s, over 30,000 German emigrants were lured to Russia to settle its barren, lawless Volga frontier. Known as the Volga Germans, these settlers survived against all odds only to have their relationship with Russia go sour in the 1870s. Many decided to emigrate again to the U.S. Among them was the Reiswig family. Their descendants include John Reiswig and his 14 children. The family survived the Dust Bowl and Depression only to face a more relentless plight: 11 of the children, plus John himself, developed Alzheimer’s in their 40s and 50s. Over a dozen other Volga German families had the same fate. In these families, researchers first realized that early-onset Alzheimer’s, a rare type of Alzheimer’s, is dominantly inherited. This discovery paved the way for genetic studies that in turn shed light on the common, late-onset type of Alzheimer’s, which is not inherited but has its own genetic component.
Illustration of a portage by the colonists en route to the settlement area on the lower Volga River. Source: “Das Manifest der Zarin” by Victor Aul.
In the summer of 2021, FDA approved an Alzheimer’s medicine: aducanumab (brand name Aduhelm). This is the first FDA-approved drug that attempts to get at the root of the disease rather than merely suppressing symptoms. However, the approval is rather controversial. Aducanumab is a vaccine that inoculates us against beta-amyloid, the protein fragment that is assumed to clump together in the brain and cause Alzheimer’s. But this assumption has not been proven: in other words, there is not a straightforward connection between reduced beta-amyloid and improved cognition. The clinical data of aducanumab are also full of dramatic twists: phase 2 trial was hailed a “game changer,” but wait, it enrolled too few people to prove cognitive effect; phase 3 trials were announced a failure and terminated, but wait, they (well, one of them) actually worked?!
These are the stories that I tell in Mind Thief: The Story of Alzheimer’s (Columbia University Press, 2021, 2022), a popular science non-fiction book that offers a comprehensive and engaging history of Alzheimer’s. Beginning with the discovery of “presenile dementia” in the early twentieth century, I examine over a century of research and controversy, covering leading hypotheses for what causes Alzheimer’s and discussing each hypothesis’s origins, merits, and gaps.
— Han Yu, Professor