Alternative strategies to delay neurodegeneration in Alzheimer's disease

 

A new study shows that increasing norepinephrine reduces markers of neuroinflammation in patients with mild cognitive impairment (MCI)
.

 

 

"EurekAlert" December 22 news

 

Raising levels of the neurotransmitter norepinephrine with atomoxetine (a drug used to treat ADHD) may prevent the Neurodegeneration in people with early signs of Alzheimer's disease
.

The findings were recently published in the journal Brain

Boosting levels of the neurotransmitter norepinephrine with atomoxetine (a drug used to treat ADHD) may be able to stop neurodegeneration in people with early signs of Alzheimer's Brain

 

Research published in the journal Brain (latest impact factor: 13.
501) on December 17, 2021

 

This is one of the first published clinical studies showing significant effects on the protein Tau, which forms neurofibrillary tangles in the Alzheimer's brain
.

In 39 patients with mild cognitive impairment (MCI), 6 months of atomoxetine treatment reduced Tau levels in the study participants' cerebrospinal fluid (CSF) and normalized other neuroinflammatory markers

In 39 patients with mild cognitive impairment (MCI), 6 months of atomoxetine treatment reduced Tau levels in study participants' cerebrospinal fluid (CSF) and normalized other neuroinflammatory markers

 

The study points to an alternative drug strategy for Alzheimer's disease that does not rely on antibodies against Tau or another Alzheimer's-related protein, beta-amyloid
.

A recently FDA-approved drug, adacanumab, targets beta-amyloid, but its benefits are debated among experts in the field

 

Emory University researchers concluded that larger, longer studies of atomoxetine in MCI and Alzheimer's disease are warranted
.

The drug had no significant effect on cognition or other clinical outcomes, which is expected given the relatively short duration of the study

Larger, longer study of atomoxetine in MCI and Alzheimer's disease necessary

 

"A major advantage of atomoxetine is that it is FDA-approved and known to be safe," said senior author David Weinshenker, PhD, professor of human genetics at Emory University School of Medicine .
The beneficial impact of CSF inflammatory markers warrants optimism
.

"

Beneficial effects of atomoxetine on brain network activity and markers of CSF inflammation warrant optimism

 

Professor David Weinshenker

 

"We are encouraged by the trial results," said lead author Allan Levey, professor of neurology at Emory University School of Medicine and director of the Goizueta Institute @Emory Brain Health.
" This treatment is safe and resistant to patients with mild cognitive impairment.
It is well-recepted and modulates the brain neurotransmitter norepinephrine as we hypothesized
.

Furthermore, our exploratory studies have shown promising results in imaging and cerebrospinal fluid biomarkers, requiring treatment over a longer period of time follow up in larger studies

This treatment is safe, well tolerated in patients with mild cognitive impairment, and modulates the brain neurotransmitter norepinephrine as we hypothesized

 

Allan Levey Director

 

Researchers at Emory University chose atomoxetine, sold in the form of Strattera, to boost levels of norepinephrine in the brain, which they believe stabilizes a vulnerable area of ​​the brain and protects against alpha Neurodegeneration associated with Zheimer's disease
.

 

Norepinephrine is primarily produced by the locus coeruleus, an area of ​​the brainstem that appears to be the first to show Alzheimer's disease-related pathology -- even in healthy middle-aged people
.

Norepinephrine is thought to reduce inflammation and promote the removal of protein aggregates, such as beta-amyloid and Tau, by garbage-clearing cells called microglia

Increased norepinephrine levels have positive effects on cognition and pathology in mouse and rat models of Alzheimer's disease

 

"We found that atomoxetine significantly increased cerebrospinal fluid norepinephrine levels in these patients, which seems obvious but absolutely necessary," Weinshenker said.
"With many drugs and trials, it is difficult to demonstrate target engagement
.

We were able to Directly assess target engagement

 

Weinshenker also emphasized that the trial stems from preclinical studies in animal models, which demonstrate the potential of norepinephrine
.

 

atomoxetine

 

The Emory University study was conducted between 2012 and 2018 and used a crossover design, in which half of the group received atomoxetine for the first six months and the other half received a placebo—and then the individuals switched
.

Participants who received atomoxetine for the first six months may have experienced carryover effects after treatment was discontinued, so their second six-month period was not necessarily a pure placebo
.

 

Study participants were all diagnosed with mild cognitive impairment and had markers in their cerebrospinal fluid of potential progression to Alzheimer's disease, based on measurements of Tau and beta-amyloid
.

 

The researchers measured the levels of dozens of proteins in the participants' cerebrospinal fluid, and the reduction in Tau after atomoxetine treatment was small -- about 5 percent over six months -- but if it persisted, it could have a significant impact on Alzheimer's.
The pathology of Haimer's disease has a greater impact
.
No significant effect on beta-amyloid was observed
.

The researchers measured the levels of dozens of proteins in the participants' cerebrospinal fluid, and the reduction in Tau after atomoxetine treatment was small -- about 5 percent over six months -- but if it persisted, it could have a significant impact on Alzheimer's.
The pathology of Haimer's disease has a greater impact
.
No significant effect on beta-amyloid was observed
.

 

Emory Brain Health Center

 

In addition, in participants taking atomoxetine, the researchers were able to detect increased metabolism in the medial temporal lobe, which is critical for memory,
by PET brain imaging .

Increased metabolism in the medial temporal lobe, which is essential for memory

 

Study participants started with a low dose of atomoxetine and gradually increased to higher doses, up to 100 mg per day
.
The participants did experience weight loss (average 4 pounds) and heart rate increases (about 5 beats per minute) while taking atomoxetine, but their blood pressure did not rise significantly
.
Some people have reported side effects, such as gastrointestinal symptoms, dry mouth, or dizziness
.

 

 

 

The FDA approved atomoxetine in 2002 to treat ADHD (attention deficit hyperactivity disorder) in children and adults, and the drug has been shown to be safe in older adults
.
It is considered to have a lower abuse potential than conventional stimulants commonly used in ADHD
.
 

The drug has been shown to be safe for older adults

 

Going forward, MRI technology can now be used to visualize the integrity of the locus coeruleus in living people, so this could be an important part of larger follow-up studies, Weinshenker said
.
The effects of atomoxetine were recently studied in Parkinson's disease patients - the benefit appears to be greater in patients with reduced locus coeruleus integrity
.

 

Emory University was founded in 1836

references

- END -

leave a message here