What word comes to mind when you hear the words Alzheimer'sdisease? Most people think aging, and they're mostly right.

Alzheimer's is, of course, a senile dementia that commonly strikesthe old, 70 and above, and accentuates as they continue to age.

Yet, there's more to aging than can be measured in years alone. Aform of progeria called Hutchinson-Gilford syndrome, for example,strikes a child at age one. By age 10, he looks like a man of 60,balding, wizened, parchment-skinned, with arteriosclerosis and heartdisease _ but not dementia. Most victims of this premature old agedie before they reach 30.

So it is with early-onset Alzheimer's disease, in which symptoms maybegin as early as age 30 to 50. What causes this precocious form ofAlzheimer's that's different from the etiology of late-onsetAlzheimer's? Separate mutant genes are implicated in each.

The gene for apolipoprotein E4 (APOE4) has been long known tocorrelate 40 to 50 percent with late-onset Alzheimer's. (SeeBioWorld Today, Nov. 17, 1994, p. 1.) More recently, a pair ofmutant genes called presenilin-1 and presenilin-2, on humanchromosome 14, apparently coincide with early-onset Alzheimer's.(See BioWorld Today, Feb. 21, 1996, p. 1.)

But appearances can deceive.

Neuropsychiatrists at Washington University in St. Louis, withcolleagues at the University of South Florida, Tampa and in the U.K.,set out to see if a polymorphism in PS-1, the presenilin-1 gene, mighthave a role in late-onset Alzheimer's as well.

They collected blood samples from 208 white male and femaleindividuals in their late 70s, diagnosed with Alzheimer's-typedementia, and 185 age-matched controls. In a separate cohort theytook blood from 29 septuagenarian African-American patients ofboth sexes, plus controls.

All clinical centers contributing subjects to the study have a trackrecord averaging 96-percent accuracy in diagnosing Alzheimer's,confirmed by post-mortem follow-ups.

In both white and black Alzheimer's groups, homozygosity _ adouble dose of the PS-1 gene, one allele from each parent _ doubledthe risk for late-onset Alzheimer's. And in the white group, "PS-1accounted for about half as much of the risk for late-onsetAlzheimer's as did APOE4."

The Lancet for March 2, 1996, reports their study under the title:"Genetic association between intronic polymorphism in presenilin-1gene and late-onset Alzheimer's disease."

Its authors offer the view that "all cases of Alzheimer's disease sharecommon pathogenic mechanisms and that PS-1 is part of thisbiochemical pathway." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.