The nerve cells in a healthy brain form a dense "neuron forest."
Alzheimer’s disease attacks brain nerve cells (neurons).
Though they may live in dread of it, most people will never develop it. "There's a 10 to 15 percent chance, if you live a normal life [span], you'll develop Alzheimer's disease," says Norman Relkin, associate professor of clinical neurology and neuroscience at New York Presbyterian Hospital and Weill Cornell Medical College. (To be sure, the prevalence in people over age 90 rises to nearly 1 in 2.) Relkin suspects the body has natural defenses—and several years ago, he and his colleagues set about finding them.
They looked for signs of antibodies that target beta-amyloid, a protein fragment that clumps in the brain plaques of Alzheimer's patients, to block the signaling pathways and eventually tunnel in to kill the cells. By comparing the blood of Alzheimer's patients with that of normal older people, the team discovered that the patients did indeed have lower-than-normal levels of a particular antibody. The researchers administered the antibody—already present in a therapy used to treat immune deficiencies—to a handful of people with Alzheimer's in 2004. A few months later, they were shocked by the improvements in the patients' cognitive function. "The mental scores were increasing by an amount that was equivalent to setting the disease back by a year and a half," Relkin says. Last June, he discovered that the antibodies were ignoring single amyloid molecules and kicking in only to destroy the toxic clumps. Relkin hopes to launch larger trials in patients this year after the Food and Drug Administration reviews his proposal.
New directions. Immunotherapy for Alzheimer's patients is just one of several new directions promising to transform the treatment of Alzheimer's, Relkin says. "We're at a juncture now where we're trying to make the transition from treating symptoms to disease-modifying treatments" that hit at the cause of Alzheimer's, he says. "A whole new window is opening in terms of the approach to the disease." Other researchers, for example, are looking at drugs that target enzymes involved in the clumping of beta-amyloid proteins.
Strides are being made on the diagnostic front, too. Until recently, doctors weren't able to say for sure whether someone had Alzheimer's until an autopsy. But the closer science comes to a treatment for Alzheimer's, the more important early detection becomes. The National Institute on Aging is currently sponsoring a study of 800 older people—some cognitively normal, some with Alzheimer's, some with mild cognitive impairment—to uncover early warning signs. Promising techniques include MRIs used to show abnormal shrinking of the brain; pet scans to detect amyloid plaques in the brain or to spot patterns of glucose use associated with Alzheimer's; or spinal taps to look for abnormal concentrations of certain proteins in the cerebrospinal fluid during the early stages of Alzheimer's.
Of course, until scientists find a treatment, early diagnosis may be more disturbing than enlightening. "The push for early diagnosis," says Columbia University's Yaakov Stern, "is predicated on the idea that we'll have something to do about [the disease] when we find it."
