Mitochondrial dysfunction present early in Alzheimer's, before memory loss

February 29, 2012

Mitochondria -- subunits inside cells that produce energy -- have long been thought to play a role in Alzheimer's disease. Now Mayo Clinic researchers using genetic mouse models have discovered that mitochondria in the brain are dysfunctional early in the disease. The findings appear in the journal PLoS ONE.

The group looked at mitochondria in three mouse models, each using a different gene shown to cause familial, or early-onset, Alzheimer's disease. The specific mitochondria changes corresponded with the mutation type and included altered mitochondrial movement, structure, and energy dynamics. The changes happened in the brain even before the mice showed any symptoms such as . The group also found that the mitochondrial changes contributed to the later loss of mitochondrial function and the onset and progression of Alzheimer's disease.

"One of the most significant findings of this study is our discovery of the impact of mitochondrial dysfunction in Alzheimer's disease," says Eugenia Trushina, Ph.D., Mayo Clinic and senior investigator on the study. "We are asking: Can we connect the degree of mitochondrial dysfunction with the progression of symptoms in Alzheimer's disease?"

Enlisting the expertise of Mayo researcher Petras Dzeja, Ph.D., the team applied a relatively new method called , which measures the chemical fingerprints of in the cell — sugars, lipids, nucleotides, amino acids and fatty acids, for example. It assesses what is happening in the body at a given time and at a fine level of detail, giving scientists insight into the cellular processes that underlie a disease. In this case, the metabolomic profiles showed changes in metabolites related to mitochondrial function and energy metabolism, further confirming that altered mitochondrial energetics is at the root of the disease process.

The researchers hope that the panel of metabolomic biomarkers they discovered can eventually be used for early diagnosis, treatment, and monitoring of Alzheimer's progression.

"We expect to validate metabolomic changes in humans with Alzheimer's disease and to use these biomarkers to diagnose the disease before symptoms appear -- which is the ideal time to start treatment," Dr. Trushina says.

The team looked at neurons of three different genetic animal models of Alzheimer's disease. Researchers applied a mitochondria-specific dye and observed their motion along axons, a process called axonal trafficking. They showed that even in embryonic neurons afflicted with Alzheimer's disease, well before the mice show any memory loss, mitochondrial axonal trafficking is inhibited. Using a panel of techniques that included electron and light microscopy, they determined that in the brains of with Alzheimer's disease, mitochondria tended to lose their integrity, ultimately leading to the loss of function. Importantly, dysfunctional were detected at the synapses of neurons involved in maintaining memory.

"We are not looking at the consequences of Alzheimer's disease, but at very early events and molecular mechanisms that lead to the disease," Dr. Trushina says. The next step is looking at the same mitochondrial biomarkers in humans, she says. As the researchers begin to understand more about the mitochondrial dynamics that are altered in Alzheimer's disease, they hope to move on to designing drugs that can restore the abnormal bioenergetics and mitochondrial dynamics to treat the disease.

Explore further: Researchers study mitochondrial function, potential new therapeutic target for Alzheimer's disease

Related Stories

Researchers study mitochondrial function, potential new therapeutic target for Alzheimer's disease

February 15, 2012
Researchers at Rush University Medical Center are conducting an early phase clinical trial of a novel drug therapy for patients with dementia due to Alzheimer's disease. The drug is a new compound called MSDC-0160, which ...

Why do neurons die in Parkinson's disease?

November 10, 2011
Current thinking about Parkinson's disease is that it's a disorder of mitochondria, the energy-producing organelles inside cells, causing neurons in the brain's substantia nigra to die or become impaired. A study from Children's ...

Recommended for you

Lifestyle changes to stave off Alzheimer's? Hints, no proof

July 20, 2017
There are no proven ways to stave off Alzheimer's, but a new report raises the prospect that avoiding nine key risks starting in childhood just might delay or even prevent about a third of dementia cases around the world.

Blood test identifies key Alzheimer's marker

July 19, 2017
A new study led by researchers at Washington University School of Medicine in St. Louis suggests that measures of amyloid beta in the blood have the potential to help identify people with altered levels of amyloid in their ...

Steering an enzyme's 'scissors' shows potential for stopping Alzheimer's disease

July 19, 2017
The old real estate adage about "location, location, location" might also apply to the biochemical genesis of Alzheimer's disease, according to new research from the University of British Columbia.

Brain scans may change care for some people with memory loss

July 19, 2017
Does it really take an expensive brain scan to diagnose Alzheimer's? Not everybody needs one but new research suggests that for a surprising number of patients whose memory problems are hard to pin down, PET scans may lead ...

Can poor sleep boost odds for Alzheimer's?

July 18, 2017
(HealthDay)— Breathing problems during sleep may signal an increased risk for Alzheimer's disease, a trio of studies suggests.

Hearing is believing: Speech may be a clue to mental decline

July 17, 2017
Your speech may, um, help reveal if you're uh ... developing thinking problems. More pauses, filler words and other verbal changes might be an early sign of mental decline, which can lead to Alzheimer's disease, a study suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.