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n the pathology lab, Nelson starts pulling microscope slides from a yellow plastic box. Tere are more than 1,400 of such boxes in the UK brain bank, each box containing the samples of a single brain, revealing the details of its cellular anatomy on onionskins of tissue. Nelson fts a slide onto a microscope and points out the neurofbrillary tangles — deep brown clumps of weeds inside cells made of a protein called tau. Another slide shows plaques, like black scabs, pushing the tissue out of the way, each scab making a Swiss cheese of the surrounding terrain. Tese two are Alzheimer's hallmarks, although their precise role in disease isn't entirely understood. Ten Nelson pulls out another slide, this one showing signs of an entirely diferent disease, something called dementia with Lewy bodies, a cognitive ailment that includes some of the rigid movement that accompanies Parkinson's. Two diseases, one brain. Tat's the norm. Tese are more than anonymous brains. Tey are connected to the years of testing that donor volunteers agree to. Once a year, Tom Conley and other prospective donors spend a half-day at BrownSanders for a mini physical and what Conley describes as "a grueling mental test." "I'm competitive enough that I want to try to do my absolute best to get all these things correct," Conley says. "I also want to know how I compare to other people. But they won't tell me how I did, period." Te results of this annual testing, combined with post-mortem exams, pushes knowledge forward, step by slow step. It's how researchers can correlate clinical judgment to biologic reality. UK's is one of 30 National Institutes of Health-designated Alzheimer's brain banks and has been around since 1984. Te Sanders in the name is actually Col. Harland Sanders. Brown is John Y. Brown Sr., whose son, former governor and former Kentucky Fried Chicken owner John Y. Brown Jr., donated money, through his foundation, toward construction of the Limestone Street building in 1972. Every day of the week, including holidays and weekends, the center sends an average of 7.7 brain samples to researchers all over the world. Tat's 14,000 samples of Kentucky brains every year. Nelson came to UK seven years ago from the University of Pennsylvania for a courtesy interview and decided to stay when he saw what UK had. "I couldn't believe what has been built here," he says. Not long after he arrived, laboratory staf member Wang-Xia Wang made a discovery that is leading to a potential Alzheimer's treatment. Volunteers are being recruited to enter a trial using the drug gemfbrozil, an FDA-approved cholesterol-lowering agent. Gemfbrozil acts on a bit of genetic material that plays doorstop to other genes. In the earliest stages of Alzheimer's, levels of this genetic material, called microRNA-107, fall. With microRNA-107 out of the picture, levels of the brain protein it used to block increase. Tis protein is believed to be responsible for higher levels of those nasty, scabby amyloid plaques. Seventy-two people at risk of developing Alzheimer's disease will be recruited for this proof-of-concept study to determine if the drug has the Alzheimer's impact they're hoping for. "Tis particular drug targets the earliest stages of the disease," says Jicha, who will act as the principal investigator in the drug trial. If it's efective, he says, "we think it would confer natural protection." Because gemfbrozil already has FDA approval for another use, several barriers to its approval in Alzheimer's will be easier to leap if the drug works as hoped. "Tis could move through the drug-discovery pipeline at a dizzying rate," Jicha says. It's one of several clinical trials ongoing at UK. Tom Conley is involved in a small proof-of-concept study testing a drug used in epilepsy and bipolar disorder known as valproic acid. Tis test in people without Alzheimer's disease is only to determine drug safety. Ultimately, the drug could be tested as an Alzheimer's preventive agent. For Conley, taking part in the trial, and doing whatever he can to help the center, is just doing his part. "I originally did it because I felt like, if (Nancy) has it, there is a reasonable chance our two girls could get it. We also have four grandchildren. If I can do something to help so that our children or grandchildren don't get it, then it's worth it." Still, he's not worried about the future, and he's not worried about Nancy. "She's always been a very strong person. Tat's one of the things that attracted me to her. She just meets problems as they happen and deals with them." She was the owner of the store Bluegrass Frames, on Taylorsville Road near Jefersontown. "We frame anything and anybody," she cracks. Now, one of her daughters runs the business. Nancy cannot remember recipes well enough to cook, Tom Conley says. As he talks, Nancy mouths the words "I don't want to cook!" Nancy, who says she feels as normal as she ever did, isn't scared. "I don't ever remember being afraid," she says. When she was a youngster, she contracted polio, and in fact, in 1947 became the second national March of Dimes poster child. She and her husband have a wall in their basement devoted to photographs of her year as poster child, including a framed version of the original poster showing little Nancy working a child-sized walker — something she never used in real life. She did, however, have pain, and still walks with a slight limp. "When you start out having polio, you learn what you have to do. I've never been afraid," she says. For all his optimism, Tom can't help staying vigilant. Tere have been losses enough. Nancy cannot remember recipes well enough to cook, he says. As Tom talks, Nancy mouths the words "I don't want to cook!" When Tom says he does the cooking these days, she mimes wild applause. "Every now and then, something will happen that will scare me," Tom admits. Returning home from an errand on a rare day when he didn't bring Nancy along, he saw her out getting some exercise in their neighborhood. She's 72 and looks great. She's slender, with short blond hair and blue eyes she uses like exclamation points. "I stopped the truck and said, 'Hey, you want a ride?'" recalls Tom. Nancy looked at him with a mixture of puzzlement and alarm and asked, "Who are you?" "I said, 'Do you want a ride home?' And she said again, 'Who are you?' "I thought, one more time. I said, 'I'm your husband. Do you want a ride home?' And she said, 'Who are you?' And now I'm thinking, oh damn! I'm in trouble now. Tis is bad." As Tom tells the story, Nancy is shifting in her seat, nearly wiggling. Her eyes open wide; she is signaling to me about something. She raises her hand to her mouth, as though whispering a secret so Tom cannot see it and mouths the words "I was lying." "She was fooling around!" Tom says almost simultaneously. Nancy throws her head back and hoots. Tom, until that moment the most serious of serious men, cracks a smile. 11.13 LOUISVILLE MAGAZINE 43