Scientists Make Strides Toward Defining Genetic Signature Of Alzheimer's Disease
Scientists have new information about the complex genetic signature associated with Alzheimer's disease, the leading cause of cognitive decline and dementia in the elderly. The research, published by Cell Press in the January issue of the American Journal of Human Genetics, uses a powerful, high-resolution analysis to look for genes associated with this devastating neurodegenerative disorder.
Previous research linked late-onset Alzheimer's disease, the most common form, with the apolipoprotein E gene. However, the genetics of the disease are complex and are not well understood. "Though apolipoprotein E has been universally confirmed as a risk gene for late-onset Alzheimer's disease, the gene is neither necessary nor sufficient to cause AD and as much as 50% of the genetic risk effect remains unexplained," says senior study author Dr. Margaret A. Pericak-Vance from the Miami Institute for Human Genomics at the University of Miami in Florida.
To gain further insight into the genetics of late-onset Alzheimer's disease, Dr. Pericak-Vance and colleagues completed a sophisticated and comprehensive genetic analysis of 492 late-onset Alzheimer's disease patients and 498 control individuals. The analysis was powerful enough to detect single nucleotide polymorphisms (SNPs) that are significantly more prevalent in individuals with Alzheimer's disease than they are in controls. A SNP is a variation of a single nucleotide of DNA.
The researchers confirmed the known apolipoprotein E association and identified a new association with a SNP on chromosome 12q13. The SNP is close to the gene for the vitamin D receptor, which has previously been linked with memory performance. "There is no known connection between this SNP and the vitamin D receptor, but the region between the two is largely uncharacterized, and it is possible that our SNP is in a region that may play some sort of regulatory role," offers Dr. Jonathan Haines, co-director of the project at Vanderbilt University's Center for Human Genetics Research.
The team also identified four other regions of interest and validated several candidate genes that exhibited a promising genome-wide association with Alzheimer's disease. "Detailed functional examination of these signals and genes may lead to a better understanding of the complex pathophysiology of Alzheimer's disease," concludes Dr. Pericak-Vance.
The researchers include Gary W. Beecham, University of Miami, Miami, FL; Eden R. Martin, University of Miami, Miami, FL; Yi-Ju Li, Duke University Medical Center, Durham, NC; Michael A. Slifer, University of Miami, Miami, FL; John R. Gilbert, University of Miami, Miami, FL; Jonathan L. Haines, Vanderbilt Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN; and Margaret A. Pericak-Vance, University of Miami, Miami, FL
“You wait till Larry comes and I tell him my theory!” The bids, duly sealed, were given into the keeping of the commissary officer to be put in his safe, and kept until the day of judgment, when all being opened in public and in the presence of the aspirants, the lowest would[Pg 188] get the contract. It was a simple plan, and gave no more opportunity for underhand work than could be avoided. But there were opportunities for all that. It was barely possible—the thing had been done—for a commissary clerk or sergeant, desirous of adding to his pittance of pay, or of favoring a friend among the bidders, to tamper with the bids. By the same token there was no real reason why the commissary officer could not do it himself. Landor had never heard, or known, of such a case, but undoubtedly the way was there. It was a question of having the will and the possession of the safe keys. "Well, I believe our boys 's all right. They're green, and they're friskier than colts in a clover field, but they're all good stuff, and I believe we kin stand off any ordinary gang o' guerrillas. I'll chance it, anyhow. This's a mighty valuable train to risk, but it ought to go through, for we don't know how badly they may need it. You tell your engineer to go ahead carefully and give two long whistles if he sees anything dangerous." "Fine-looking lot of youngsters," he remarked. "They'll make good soldiers." "That's just what he was, the little runt, and we had the devil's own time finding him. What in Sam Hill did the Captain take him for, I'd like to know? Co. Q aint no nursery. Well, the bugler up at Brigade Headquarters blowed some sort of a call, and Skidmore wanted to know what it meant. They told him that it was an order for the youngest man in each company to come up there and get some milk for his coffee tomorrow morning, and butter for his bread. There was only enough issued for the youngest boys, and if he wanted his share he'd have to get a big hustle on him, for the feller whose nose he'd put out o' joint 'd try hard to get there ahead o' him, and get his share. So Skidmore went off at a dead run toward the sound of the bugle, with the boys looking after him and snickering. But he didn't come back at roll-call, nor at tattoo, and the smart Alecks begun to get scared, and abuse each other for setting up a job on a poor, innocent little boy. Osc Brewster and Ol Perry, who had been foremost in the trick had a fight as to which had been to blame. Taps come, and he didn't get back, and then we all became scared. I'd sent Jim Hunter over to Brigade Headquarters to look for him, but he came back, and said they hadn't seen anything of him there. Then I turned out the whole company to look for him. Of course, them too-awfully smart galoots of Co. A had to get very funny over our trouble. They asked why we didn't get the right kind of nurses for our company, that wouldn't let the members stray out of their sight? Why we didn't call the children in when the chickens went to roost, undress 'em, and tuck 'em in their little beds, and sing to 'em after they'd said 'Now I lay me down to sleep?' I stood it all until that big, hulking Pete Nasmith came down with a camp-kettle, which he was making ring like a bell, as he yelled out, 'Child lost! Child lost!' Behind him was Tub Rawlings singing, 'Empty's the cradle, baby's gone.' Then I pulled off my blouse and slung it into my tent, and told 'em there went my chevrons, and I was simply Scott Ralston, and able to lick any man in Co. A. One o' their Lieutenants came out and ordered them back to their quarters, and I deployed the company in a skirmish-line, and started 'em through the brush toward Brigade Headquarters. About three-quarters o' the way Osc Brewster and Ol Perry, when going through a thicket, heard a boy boo-hooing. They made their way to him, and there was little Skidmore sitting on a stump, completely confused and fagged out. He'd lost his way, and the more he tried to find it the worse he got turned around. They called out to him, and he blubbered out: 'Yes, it's me; little Pete Skidmore. Them doddurned fools in my company 've lost me, just as I've bin tellin' 'em right along they would, durn 'em.' Osc and Ol were so tickled at finding him that they gathered him up, and come whooping back to camp, carrying him every step of the way." And the rush stopped. Cadnan waited for a second, but there was no more. "Dara is not to die," he said. Then he saw Orion hanging over him, very low in the windy sky, shaking with frost. His eyes fixed themselves on the constellation, then gradually he became aware of the sides of a cart, of the smell of straw, of the movement of other bodies that sighed and stirred beside him. The physical experience was now complete, and soon the emotional had shaped itself. Memory came, rather sick. He remembered the fight, his terror, the flaming straw, the crowd that constricted and crushed him like a snake. His rage and hate rekindled, but this time without focus—he hated just everyone and everything. He hated the wheels which jolted him, his body because it was bruised, the other bodies round him, the stars that danced above him, those unknown footsteps that tramped beside him on the road. Farewell to Jane and Caroline!" HoME大香蕉色人阁
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