Alzheimer's disease and amyloid

According to The New York Times, "A study of a rare gene mutation that protects people against Alzheimer’s disease provides the strongest evidence yet that excessive levels of a normal brain substance, beta amyloid, are a driving force in the disease — bolstering hopes that anti-amyloid drugs already under development might alter the disease’s course or even prevent it." In Genetic Twists of Fate, Stanley Fields and Mark Johnston's discussion of the history of Alzheimer’s research includes mention of Martin Roth, Bernard Tomlinson, and Gary Blessed's 1970s demonstration that the degree of dementia in a person correlated with the number of amyloid deposits in the brain. Here's an excerpt from the book:

In late 1906, Dr. Alois Alzheimer presented his paper on “profound dementia in a young adult.” He concluded, “I have just presented a clearly defined and hitherto unrecognized disorder.” By all accounts, Alzheimer’s presentation had no impact on the audience of psychiatrists who heard it.

Because Auguste [Deter] displayed symptoms at only fifty-one years of age, her disease—dubbed Alzheimer’s disease a few years later by Alzheimer’s mentor, Emil Kraepelin, the father of modern psychiatry—was classified as a presenile dementia, defined then as occurring before sixty years of age. This disorder stood in contrast to the much more common senile dementia displayed by older patients. This distinction between dementia in a younger person and dementia in the aged would confound the field for half a century, during which time Alzheimer’s disease attracted hardly any attention from researchers.

Whereas presenile dementia showed characteristics that caused it to be considered a disease, senile dementia was thought to be the result of the normal deterioration of old age. Instead of giving credence to the idea of a physical illness, psychiatrists fostered a model of dementia in the aged that pinned the cause on some combination of personality, emotional trauma, mandatory retirement, social isolation, and the breakup of the family. In the 1940s and 1950s they linked social pathology to brain pathology, viewing the former as the cause of the latter. To psychiatrists of that era, it was all nurture, and no nature.

By the 1970s, however, society had come to appreciate that people should not be discriminated against on the basis of their advanced age any more than because of their race or sex. As a consequence, the stereotype of aging individuals as inevitably succumbing to dementia began to fade. Meanwhile, on the scientific front, Martin Roth, Bernard Tomlinson, and Gary Blessed at Newcastle University, in the U.K., demonstrated that the degree of dementia in a person correlated best not with age but with the number of deposits of amyloid and neurofibrillary tangles observed in the brain, suggesting that specific pathological changes, and not the general aging process, were the culprit. Because the clinical and pathological manifestations of the early-onset (presenile) and late-onset (senile) dementias were the same, both disorders were classified as Alzheimer’s disease.

These findings led to a much greater realization of the burden of Alzheimer’s disease, which until then had been thought to be relatively small. In 1976, Robert Katzman of the University of California in San Diego made the bold estimate that Alzheimer’s disease afflicted 1.2 million Americans and accounted for sixty thousand to ninety thousand deaths each year. Those numbers startled the public and galvanized the research community, stimulating big increases in funding for research into the causes of the disease and the development of therapies. The numbers from thirty years ago pale compared to those of today: about 5 million Americans currently suffer from this horrible disease; by 2050 it is expected to be between 11 million and 16 million.