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A key argument supporting the theory linking aluminium with Alzheimer’s
disease may have been overturned. Å®ÉúСÊÓƵs in Oxford have shown that senile
plaques – characteristic features of the brains of people with Alzheimer’s
– do not contain significant amounts of aluminium. Instead, the Oxford team
believes, the aluminium that others said they had found may simply have
been a contaminant of the dyes used to stain brain tissue for analysis.

Judith Landsberg, Frank Watt and their colleagues at the University
of Oxford’s scanning proton microprobe unit and the Radcliffe Infirmary,
studied 105 samples of brain tissue from five people who had died of Alzheimer’s
and two elderly people who had died from other causes, whose brain tissues
were used as controls. The team found aluminium in fewer than 10 per cent
of the cores of senile plaques. They also found the metal in tissue outside
the cores and in the control tissue, which suggests that it may simply be
background contamination (Nature, 5 November, p 65).

‘We found aluminium when we were staining and we find much less when
we look at unstained tissues,’ says Geoff Grime, a member of the Oxford
team and co-founder of the scanning unit. ‘One of the cornerstones of the
aluminium and Alzheimer’s theory has been the finding of aluminium in senile
plaques, and we have just pulled that out.’

Other teams, for example a group at the University of Newcastle led
by John Candy and Jim Edwardson, have repeatedly found aluminium in the
cores of senile plaques. During the late 1980s, their findings were widely
accepted as strong evidence for a link between the metal and the disease.
But controversy between scientists has grown stronger as different scanning
techniques and laboratories have produced different results (This Week,
21 July 1990).

The Oxford team’s methods exploit the scanning proton microscope, which
fires a beam of energetic protons through the sample material. The protons
collide with electrons and with nuclei in the atoms and these interactions
provide detailed and precise information about the material (see ‘Microscopes
with proton power’, New Å®ÉúСÊÓƵ, 1 June 1991). Others have used lasers
and secondary ion mass spectrometry.

Unlike all previous analyses, the Oxford team’s latest study was performed
on untreated brain tissue. Until now, scientists have been forced to treat
the tissue with reagents to distinguish the plaques from surrounding tissue.

However, Landsberg had shown previously that even the purest reagents
available contained aluminium. ‘This caused doubt in our minds as to whether
the aluminium was being poured onto the tissue in the reagents,’ says Grime.
So the Oxford group tried to work out how to analyse brain tissue without
staining it.

Their approach exploited two techniques. To distinguish the plaques
from their surrounding tissue, they used a technique known as STIM, short
for scanning transmission ion microscopy. This uses the proton microscrope
to provide a ‘contour map’ of the density of tissue, at very high resolution.
Because plaques are denser than their surrounding tissue, STIM can pick
them out. The team also used PIXE, (particle-induced X-ray emission) which
provides a map of certain elements that is sensitive to a few parts per
million. But Bob Williams, another researcher in the organic chemistry department
at Oxford, warns that there is still doubt about the variation between different
techniques. The teams that have detected aluminium are using more sensitive
techniques than the Oxford group, he says, and scientists do not know what
levels of aluminium may be harmful.

Whatever doubts Oxford results add to the aluminium theory, they do
not signal its death knell. There is clear evidence that the metal is toxic
to neurons. Also, senile plaques are only one of the characteristic features
of the Alzheimer’s brain. High levels of aluminium have been found in neurofibrillary
tangles, the other characteristic feature, by Dan Perl of the Mount Sinai
Medical Center in New York. Grime stresses that the Oxford team has not
looked at tangles.

There is more circumstantial evidence to support the aluminium theory.
One study, for example, found a slightly increased risk of Alzheimer’s in
people whose drinking water contained large amounts of the metal (This Week,
21 January 1989). But many scientists are unconvinced by such studies, and
will be waiting eagerly to see what happens next.