Alzheimer's Disease Research

Uploaded by ERANetNEURON on 06.02.2011

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Alzheimer's Disease
Alzheimer's Disease is the most common form of dementia in the elderly,
affecting about 5% of the population at the age of 65.
This increases to more than 25%
in subjects aged 85 years or more.
Alzheimer's Disease was originally described in 1907
by the German neuropathologist Alois Alzheimer
in a 51 year old woman with dementia.
The characteristic features of Alzheimer's Disease
are global cognitive disjunction,
especially loss of memory,
aphasia or speech difficulties.
These patients also show changes in personality and behavior
and lose their ability for self-care,
Such as dressing, washing and feeding.
The behavioral changes
result from a gradual shrinkage of the brain
through loss of neural-connections.
As the brain substance decreases,
the size of the ventricles increases.
Neuronal loss occurs in areas
controlling memory and language,
but also in other areas.
Memory loss is partly
due to degeneration of neurons
that release the neurotransmitter acetylcholine.
After combining with specific receptors
in the post-synaptic neuron to cause its effect,
acetylcholine is rapidly destroyed
by an enzyme called cholinesterase.
Drugs that inhibit the action of cholinesterase
improve memory and attention and reduce behavioral symptoms
in a significant proportion of patients
for up to about 2 years.
By the time Alzheimer's Disease is diagnosed,
there is already a considerable loss of brain substance
which cannot be restored.
if we want to prevent the neuronal loss and disease development,
treatment must be given at an earlier stage,
one in which the subjects
show only a mild degree of cognitive impairment
compared to those with Alzheimer's Disease.
About 40%-50% of subjects with mild cognitive impairment
develop Alzheimer's Disease within 4-5 years.
Cholinesterase inhibitors do not alter the rate of conversion
of mild cognitive impairment to Alzheimer's Disease
because they are not able to prevent
the underlying causes of the disease.
Examination of the brains of subjects with Alzheimer's Disease
and those with mild cognitive impairment
reveals the presence of chemical changes
denoted as oxidative stress that damage neurons.
Oxidative stress results from the accumulation of noxious substances
that are not eliminated efficiently in the aging brain.
The resulting neuronal damage
causes the activation of cells
with immune function called glia
to remove the cell debris.
glia also release chemical substances
like nitric oxide and cytokines,
some of which may further impair neuronal activity.
The aim of our research is to produce new drugs
that can reduce oxidative stress
and glial activation
in order to prevent the degenerative process
We test our new drugs in cell cultures
in which oxidative stress is induced
by exposing the cells to hydrogen peroxide
which damages mitochondria,
the energy source of the cell.
This can be measured by use of a special dye
which changes from red to green.
Treatment of the culture with our new drug
protects the mitochondria
which remain red, and the cells stay alive and function.
Like humans,
rats develop memory deficits as they age
and their brains show evidence of oxidative stress.
Aged rats also have
more activated glia cells than young rats.
The glia cells release damaging cytokines
as they do in patients with Alzheimer's Disease.
When middle-aged rats were treated
with the new drug for 6 months,
there was a decrease in oxidative stress
and glial activity
to the levels seen in young rats.
The drug also restored neurotrophic factors
which are essential for normal nerve activity.
Prior to the histological examination
we tested the spatial memory of the rats in a water maze,
in which we determined how many trials it took
until they could find a hidden escape platform.
Young rats learned to find the escape platform within about 20 seconds,
after only a few trials,
while the untreated old ones take much longer.
Middle-aged rats
that had been treated for several months with the new drug,
perform much better in old age
than the untreated ones,
indicating that their learning ability and spatial memory
had been largely preserved.
If this drug also prevents the development of oxidative stress
and glial activation
in human subjects with mild cognitive impairment,
it may be able to reduce the number of such subjects
that eventually develop Alzheimer's Disease.