The Forgetting: Understanding Alzheimer’s: A Biography of a Disease. David Shenk

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СКАЧАТЬ handsome young husband has disappeared and a strange elderly man has taken his place. Why is someone taking your clothes off and pouring warm water over you? How long have you been lying in this strange bed?

      By 1992, the signs of Reagan’s illness were impossible to ignore. At the conclusion of a medical exam in September, as the New York Times would later report, Reagan looked up at his doctor of many years with an utterly blank face and said, “What am I supposed to do next?” This time, the doctor knew that something was very wrong.

      Sixteen months later, in February 1994, Reagan flew back to Washington, D.C., from his retirement home in Bel Air, California, for what would turn out to be his final visit. The occasion was a dinner celebrating his own eighty-third birthday, attended by Margaret Thatcher and twenty-five hundred other friends and supporters.

      Before the gala began, the former President had trouble recognizing a former Secret Service agent whom he had known well in the White House. This didn’t come as a total shock to his wife, Nancy, and other close friends, but it did cause them to worry that Reagan might have problems with his speech that night.

      The show went on as planned. After an introduction by Thatcher, Reagan strolled to the podium. He began to speak, then stumbled, and paused. His doctor, John Hutton, feared that Reagan was about to humiliate himself. “I was holding my breath, wondering how he would get started,” Hutton later recalled, “when suddenly something switched on, his voice resounded, he paused at the right places, and he was his old self.”

      Back at his hotel after the dinner, Reagan again slipped into his unsettling new self, turning to Nancy and saying, “Well, I’ve got to wait a minute. I’m not quite sure where I am.” Though the diagnosis and public announcement were both months away, Reagan was already well along the sad path already trod by his mother, his brother, and by Auguste D.

      The doctors who diagnosed Reagan in 1994 knew with some specificity what was happening to his brain. Portions of his cerebral cortex, the thin layer of gray matter coating the outside of his brain, were becoming steadily clouded with two separate forms of cellular debris: clumpy brown spherical plaques floating between the neurons, and long black stringy tangles choking neurons from inside their cell membranes. As those plaques and tangles spread, some neurons were losing the ability to transmit messages to one another. Levels of glucose, the brain’s sole energy source, were falling precipitously, weakening cell function; neurotransmitters, the chemicals that facilitate messages between the neurons, were becoming obstructed. The tangles in some areas of the brain were getting to be so thick it was like trying to kick a football through a chain-link fence.

      Ultimately, many of the neurons would die, and the brain would begin to shrink. Because the brain is highly specialized, the strangulation of each clump of neurons would restrict a very specific function—the ability to convert recent events into reliable memories, for example, or the ability to recall specific words, or to consider basic math problems. Or, eventually, to speak at all, or recognize a loved one. Or to walk or swallow or breathe.

      We know about plaques and tangles because of Auguste D. and Alois Alzheimer. After four and a half years in the hospital, Frau D. died on April 8, 1906. Her file listed the cause as “septicaemia due to decubitis”—acute blood poisoning resulting from infectious bed sores. In her last days, she had pneumonia, inflammation of the kidneys, excessive fluid in the brain, and a high fever. On the day of her death, doctors understood no more than they had on the first day she was admitted. They could say only this about Auguste D.: that a psychic disturbance had developed in the absence of epileptic fits, that the disturbance had progressed, and that death had finally intervened.

      Alois Alzheimer wanted to learn more. He wanted to look at her brain.

      Standing apart from most doctors at the time, Alzheimer was equally interested in both clinical and laboratory work. He was known for his tireless schedule, his devoted teaching, and his own brand of forgetfulness. An inveterate smoker, he would put a half-smoked cigar down on the table before leaning into a student’s microscope for a consultation. A few minutes later, while shuffling to the next microscope, he’d light a fresh cigar, having forgotten about the smoke already in progress. At the end of each day, twenty microscopes later, students recalled, twenty cigar stumps would be left smoldering throughout the room.

      But Alzheimer did not forget about the woman who had lost herself in Frankfurt. Though he had since moved to the Royal Psychiatric Clinic, in Munich, to work for the renowned psychiatrist Emil Kraepelin, he sent for Frau D.’s central nervous system as soon as she died. Her brain, brainstem, and spinal cord were gently removed from the elaborate bone casing, that flexible yet durable wrapper that allows us all to crouch, twist, and bump into things without much concern. The exposed contents were then likely wrapped in formalin-soaked towels, packed carefully in a wooden crate, and shipped by locomotive 190 miles southeast to Munich.

      Imagine, now, that lifeless brain on a passenger train. A coconut-sized clump of grooved gelatinous flesh; an intricate network of prewired and self-adapting mechanisms perfected over more than a billion years of natural selection; powered by dual chemical and electrical systems, a machine as vulnerable as it is complex, designed to sacrifice durability for maximal function, to burn brightly—a human brain is 2 percent of the body’s weight but requires 20 percent of its energy consumption—at the cost of impermanence. Enormously powerful and potato-chip fragile at the same time, the brain is able to collect and retain a universe of knowledge and understanding, even wisdom, but cannot hold on to so much as a phone number once the glucose stops flowing. The train, an elementary device by comparison, can, with proper maintenance, be sustained forever. The brain, which conceived of the train and all of its mechanical cousins, cannot. It is ephemeral by design.

      But there was nothing in the brain’s blueprint about this sort of thing, as far as Alzheimer could infer. This was a flaw in the design, a molecular glitch, a disease process, he suspected, and it was important to see what that process looked like up close.

      It was also now actually possible to do this for the first time, thanks to a whirl of European innovation. Ernst Leitz and Carl Zeiss had just invented the first distortion-free microscopes, setting a standard in optics that survives today. Franz Nissl had revolutionized tissue-staining, making various cell constituents stand out, opening up what was characterized as “a new era” in the study of brain cells and tissues. (The “Nissl method” is still in use. Nissl, a close collaborator and friend of Alois Alzheimer, became a medical school legend with his instructions on how to time the staining process. “Take the brain out,” he advised. “Put it on the desk. Spit on the floor. When the spit is dry, put the brain in alcohol.”)

      Dr. Alzheimer’s assistants prepared for microscopic examination more than 250 slides from slivers of the outer lining (the meninges) of Frau D.’s brain; from the large cerebral vessels; from the frontal, parietal, and occipital areas of the cerebral cortex (locus of conscious thought); from the cerebellum (regulator of balance, coordination, gait) and the brainstem (breathing and other basic life functions); and from the spinal cord, all chemically preserved in a cocktail of 90 percent alcohol/10 percent formalin, and stained according to a half-dozen recipes of Alzheimer’s contemporaries.

      Having fixed, frozen, sliced, stained, and pressed the tissue between two thin pieces of glass, Alzheimer put down his cigar and removed his pince-nez, leaned into his state-of-the-art Zeiss microscope, and peered downward. Then, at a magnification of several hundred times, he finally saw her disease.

      It looked like measles, or chicken pox, of the brain. The cortex was speckled with crusty brown clumps—plaques—too many to count. They varied in size, shape, and texture and seemed to be a hodgepodge of granules and short, crooked threads, as if they were sticky magnets for microscopic trash.

      The plaques were nestled in amongst the neurons, in a space normally occupied by supporting tissue known as СКАЧАТЬ