- A research team
from Temple University has shown that 12/15-lipoxygenase is elevated in Alzheimer's disease patients.
- The study used an
inhibitor to lower the level of 12/15-lipoxygenase in Alzheimer's disease patients.
- There was
reversal of cognitive decline after the use of an inhibitor of 12/15-lipoxygenase
One of the major
symptoms associated with Alzheimer's disease is cognitive decline due to
several changes that occur in the brain along with elevated levels of the
enzyme 12/15-lipoxygenase. A startling new study has found that an inhibitor
to 12/15-lipoxygenase could reverse cognitive decline and neuropathology.
The studies were
conducted on mice with Alzheimer's disease like phenotype and were found to
reverse the symptoms of cognitive decline. The study shows promise for its
potential use in the treatment of this neurodegenerative disease.
‘Cognitive decline that cripples Alzheimer’s patients can be reversed using inhibitor of 12/15-lipoxygenase’
A research team led by
Dr. Domenico Pratic and colleagues from Temple University in Philadelphia, have
raised the hope for a possible new drug therapy for Alzheimer's disease
patients who currently are devoid of therapy options for cognitive decline.
Earlier studies have stressed on lowering the toxic level of protein buildup in
the brain that leads to the development of brain plaques, causing the death of neurons.
Dr. John Krystal who is
the editor of biological psychiatry said that this was an exciting study as the
nerve cells were taught to digest the toxic protein which would, otherwise,
cause cell death.
In the study, a triple
transgenic mouse model was used with Alzheimer's disease-like
phenotype which included cognitive decline. The study first author Antonio Di
Meco had shown earlier that 12/15-lipoxygenase inhibitor
PD146176 could stop the development of decline in cognitive ability in mice.
In order to understand
the effects of this inhibitor in the real world scenario, the study authors
allowed the mice to grow for a period of one year. Cognitive impairment and
neuropathology were established in the mice before the inhibitors 12/15-lipoxygenase
inhibitor PD146176 were injected into the
Dr. Pratico said that
their studies showed for the first time that selective inhibition of the
12/15-lipoxygenase enzyme rescued the entire Alzheimer's disease-like
Mice that were not
treated with the inhibitors showed poor learning and memory, but
mice that were treated with the inhibitors were just like normal mice with
The researchers found that treatment with
PD146176 resulted in significantly lowered levels of Aβ and insoluble tau
The mechanism of action
was autophagy where the body's natural killer cells were activated by the
inhibition of 12/15-lipoxygenase. Activation of these natural killer cells
present in the body leads to a
reduction in the levels of tau, showcasing that the inhibitor
worked by re-activating neuronal autophagy machinery which would aid in the
build-up of tau in the cells.
The study results show
that drug inhibition of 12/15-lipoxygenase reverses learning as well as
impairments in memory along with reduction in Aβ and tau neuropathology, even
after these conditions developed in the study mice.
Dr. Pratico said that
the findings of the study have important translational value and that this is a
novel method of treatment of Alzheimer's disease.
is a neurodegenerative disease
and is the most common form of dementia. It is characterized by memory loss as
well as a decline in intellectual abilities, which interfere with the
quality of life being led by the patient.
decline, is normally associated with aging. However, Alzheimer's
is not associated with aging-related mental decline. The
greatest risk factor that is associated with Alzheimer's disease is advanced
aging with the majority of people with this disease condition over the age of
A few people are found
to have early onset Alzheimer's disease that occurs when the individual is in
the 40s or 50s but most cases of Alzheimer's disease is found among people over
60 years of age. It is a progressive disease and the symptoms of dementia
worsen over a period of time. In the early stages of Alzheimer's disease, there
is a mild loss of memory but as the disease progresses; there is an
inability to carry on a conversation along with difficulty in responding to the
disease is the sixth leading cause of death in the U.S. People with the disease
condition can live for 8 years without showing any noticeable symptoms but the survival
of the patient varies from 4 to 20 years, based on age and health conditions.
The decline in cognitive
abilities cripple patients with Alzheimer's and leads to a very dependent life.
The patients will be unable to follow recipes or even perform simple tasks on
their own, requiring continuous assistance.
Previous studies have
shown that interventions could slow or prevent further mental decline but the
current study has shown a reversal of mental decline, which is a definite step
in the treatment of Alzheimer's disease.
- Antonio Di Meco, Jian-Guo Li, Benjamin E. Blass, Magid Abou-Gharbia, Elisabetta Lauretti, Domenico Pratic�. 12/15-Lipoxygenase Inhibition Reverses Cognitive Impairment, Brain Amyloidosis, and Tau Pathology by Stimulating Autophagy in Aged Triple Transgenic Mice. Biological Psychiatry, (2017); 81 (2): 92DOI: 10.1016/j.biopsych.2016.05.023
- What Is Alzheimer's? - (http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp)