Alzheimer's starts long before symptoms

[Guest guest]

Headlines 03 mar 1999 From MedServ Medical News

Alzheimer's starts long before symptoms

Written by Kathleen Stein

ST. LOUIS, March 1 (UPI) -

Long before a person suffers memory loss or other mental impairment

associated with Alzheimer's, the disease may already be in place in the brain,

according to a new study. In research appearing in the March issue of the

ls of Neurology, scientists speculate that the first physical signs of the

disease in the brain appear as much as a decade before symptoms show up.

Their findings are based on a study of autopsies that compared the brains of

people who died with normal mental function with those who had various degrees

of Alzheimer's.

They report finding the distinct physical signatures of Alzheimer's in the

brains of some subjects who had no dementia or other evidence of the disease.

" In the brains of some people with the very earliest signs of Alzheimer's, the

lesions were already firmly established at a time the disease was barely

detectable clinically, " says Dr. C. , professor of neurology at

Washington University School of Medicine in St. Louis. He says effective

therapies should be developed and initiated earlier to stop these brain

lesions before they accumulate to the point where they impair cognition.

and his Washington University colleague, ph L. Price, professor of

anatomy and neurobiology, say their discoveries were the result of a study

initiated in 1979 at the school of medicine's Alzheimer's Disease Research

Center. The study represents one of the longest observations of Alzheimer's

patients in the country. " We now follow 520 volunteer participants on an

annual basis, " says , the center's co-director. " Most suffer dementia,

but some are healthy individuals. "

The center uses its Clinical Dementia Rating scale to distinguish healthy

aging participants from those with the earliest stages of Alzheimer's. After

the participant's death, the center studies brain tissue in the hippocampus

and nearby regions, which are involved in memory processing and are vulnerable

to Alzheimer's. There, the scientists look for two disruptive signs of the

disease: beta-amyloid plaques and neurofibrillary tangles. Beta-amyloid

plaques form when a brain protein is cut in the wrong place. A tangle is a

nerve cell containing twisted and knotted filaments and an abnormal protein.

The neuroscientists also found that even participants with normal mental

function had evidence of tangles in the hippocampus. But they could find no

plaques in that group. Scrutinizing the key brain areas, Price found tangles

in even the youngest of the healthy control subjects, says . " The

youngest died at age 51. It's not as if the 51-year-old hippocampus is

devastated with them, but if one hunts, tangles can be identified even at that

age. " But brain regions of those suffering from dementia - even those in the

mildest stages of Alzheimer's - were full of plaques. This finding prompted

to conclude that " probably the best correlate of whether somebody has

Alzheimer's dementia or not is the presence of lots of amyloid plaques in a

brain area called the neocortex. "

Even the most mildly impaired subjects, presumably in the earliest stages of

the disease, already had a neocortex full of plaques. " The way our data is

shaping up, " he adds, " when amyloid is deposited in the neocortex to any

appreciable degree, it correlates with Alzheimer's. " , whose group is

investigating neuroimaging techniques to observe the hippocampus for early

warning signs of change, believes non- invasive procedures such as PET or MRI

eventually may be able to detect the plaques before the onset of clinical

evidence. Some centers are trying to tag amyloid for imaging purposes to see

when the first amyloid deposition occurs.

" I don't think anyone has developed a tag or dye yet for human experiments,

but that thinking is at the root of a number of investigations, " he says.

Drugs specifically designed to halt the deposition of amyloid plaques are also

at the cusp of human testing. and his team are currently moving from

studies of the earliest detectable signs of Alzheimer's to an examination of

very elderly people.

" The question has always been, " says, " how much is due to age alone

and how much is truly a disease. We're looking to find persons in their 90s

or even older whose brains remain free of plaques. " But the debate about the

role of amyloid plaques is hardly over. " There's no question the brain is

losing nerve cells prior to people being clinically impaired, " says A.

Kaye, an Alzheimer's investigator in the department of neurology at the Oregon

Health Sciences University in Portland. " Whether that earliest change is due

to amyloid or something else is still a big question. " In no way do I mean to

imply amyloid is not important to the process of Alzheimer's disease. But

whether it's the prime mover or prime end result of the underlying pathology

is still being debated. It's like if you were to study the cause of fires, "

Kaye adds, " and at every fire scene you'd see a pile of ashes. You might

assume that ashes cause fires, when in fact it might be something like the

gasoline whose evidence was consumed in the fire. "

=============================================================