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Unique
case study sheds light on pathological
course of Alzheimer’s
December 14, 2010-- A case study from the
Swedish medical university Karolinska
Institutet sheds light on the pathological
course of Alzheimer's disease. The brain of
the first Alzheimer's patient to display
amyloids demonstrable with a PET scanner has
been studied both during progression of the
disease and after death.
One pathological characteristic of
Alzheimer's disease is the accumulation in
the brain of beta-amyloid proteins to form
amyloid plaques. However, it is not known
how early the plaques forms in the brain,
whether they are the primary cause of the
disease or what pathogenic role is played by
other changes in the brain.
The very first PET scan in the world of
amyloid plaque in a living patient with the
amyloid-binding compound 11C-PIB was
performed in 2002 by Professor Agneta
Nordberg at Karolinska Institutet on a
56-year old Alzheimer's patient.
The researchers then monitored the patient
as the disease progressed with regular PET
scans and memory tests. After the patient
died, the team carried out pathological and
neurochemical analyses of the brain tissue.
The combined result analyses, which are now
published in the renowned neurological
journal BRAIN, give a detailed picture of
how Alzheimer's disease develops. For
example, the results show that high
concentrations of amyloid plaques were
discovered at an early stage of the disease
when the patient suffered slight memory
loss. The levels remained unchanged during
the course of the disease, in contrast to
the increasingly declining energy metabolism
in the brain, which was also measured using
PET as the patient's memory gradually
deteriorated.
One formerly unknown connection that was
discovered in the study is that the greater
accumulation of plaque is accompanied by a
reduction in the number of neuronal
nicotinic receptors in the brain. These
receptors are central to memory function,
and this new finding demonstrates that the
receptors are affected early on in the
disease development.
Further, inflammatory
changes were measured in brain regions with
low levels of plaques which suggest that the neuroinflammation related to Alzheimer's
disease might have a different cause and
evolve at different stage of the disease
compared to that of amyloid accumulation.
Studies on this are currently being carried
out on living patients using PET technology.
Today, over 1,000 patients around the world
have undergone PET scans for measuring
amyloid concentrations in the brain.
PIB-PET was recently recommended as the
earliest clinical diagnostic biomarker for
discovering Alzheimer's disease, following
the diagnostic guidelines laid out by the
American Alzheimers Association.
However, if clinicians are to gain further
insight into the importance of these PET
examinations, a follow up of the results
obtained from conducted PET studies should
be performed in the brain tissue of deceased
patients.
"If we combine different examinations, we
will be able to affirm that complex changes
take place at the same time in the brain
during the development of Alzheimer's
disease", says Professor Nordberg.
"Our
study shows that new, modern imaging
technology known as molecular imaging makes
it possible to discover the disease at an
early stage. This opens up new opportunities
for early diagnosis and for understanding
the causes of the disease and identifying
patients who can be expected to respond well
to future Alzheimer's therapy."
