Insulin is a possible new treatment for Alzheimer's

February 2, 2009,

A Northwestern University-led research team reports that insulin, by shielding memory-forming synapses from harm, may slow or prevent the damage and memory loss caused by toxic proteins in Alzheimer's disease.

The findings, which provide additional new evidence that Alzheimer's could be due to a novel third form of diabetes, will be published online the week of Feb. 2 by the Proceedings of the National Academy of Sciences (PNAS).

In a study of neurons taken from the hippocampus, one of the brain's crucial memory centers, the scientists treated cells with insulin and the insulin-sensitizing drug rosiglitazone, which has been used to treat type 2 diabetes. (Isolated hippocampal cells are used by scientists to study memory chemistry; the cells are susceptible to damage caused by ADDLs, toxic proteins that build up in persons with Alzheimer's disease.)

The researchers discovered that damage to neurons exposed to ADDLs was blocked by insulin, which kept ADDLs from attaching to the cells. They also found that protection by low levels of insulin was enhanced by rosiglitazone.

ADDLs (short for "amyloid beta-derived diffusible ligands") are known to attack memory-forming synapses. After ADDL binding, synapses lose their capacity to respond to incoming information, resulting in memory loss.

The protective mechanism of insulin works through a series of steps by ultimately reducing the actual number of ADDL binding sites, which in turn results in a marked reduction of ADDL attachment to synapses, the researchers report.

"Therapeutics designed to increase insulin sensitivity in the brain could provide new avenues for treating Alzheimer's disease," said senior author William L. Klein, a professor of neurobiology and physiology in the Weinberg College of Arts and Sciences and a researcher in Northwestern's Cognitive Neurology and Alzheimer's Disease Center. "Sensitivity to insulin can decline with aging, which presents a novel risk factor for Alzheimer's disease. Our results demonstrate that bolstering insulin signaling can protect neurons from harm."

The amyloid beta oligomers, or ADDLs, form when snippets of a protein clump together in the brain. In Alzheimer's disease, when ADDLs bind to nearby neurons, they cause damage from free radicals and a loss of neuronal structures crucial to brain function, including insulin receptors. This damage ultimately results in memory loss and other Alzheimer's disease symptoms. The Alzheimer's drug Namenda has been shown to partially protect neurons against the effects of ADDLs.

"The discovery that anti-diabetic drugs shield synapses against ADDLs offers new hope for fighting memory loss in Alzheimer's disease," said lead author Fernanda G. De Felice, a former visiting scientist in Klein's lab and an associate professor at the Federal University of Rio de Janeiro, Brazil.

"Recognizing that Alzheimer's disease is a type of brain diabetes points the way to novel discoveries that may finally result in disease-modifying treatments for this devastating disease," adds Sergio T. Ferreira, another member of the research team and a professor of biochemistry in Rio de Janeiro.

In other recent and related work, Klein, De Felice and their colleagues showed that ADDLs bound to synapses remove insulin receptors from nerve cells, rendering those neurons insulin resistant.

The outcome of the molecular-level battle between ADDLs and insulin, which in the current PNAS study was found to remove ADDL receptors, may determine whether a person develops Alzheimer's disease.

Source: Northwestern University

Explore further: Diabetes drug 'significantly reverses memory loss' in mice with Alzheimer's

Related Stories

Diabetes drug 'significantly reverses memory loss' in mice with Alzheimer's

January 1, 2018
A drug developed for diabetes could be used to treat Alzheimer's after scientists found it "significantly reversed memory loss" in mice through a triple method of action.

Researchers find pathological signs of Alzheimer's in dolphins, whose brains are much like humans'

November 14, 2017
A team of scientists in the United Kingdom and the U.S. recently reported the discovery of pathological signs of Alzheimer's disease in dolphins, animals whose brains are similar in many ways to those of humans.

How are depression and memory loss connected?

April 15, 2014
(Medical Xpress)—Past research has long indicated that depression is a big risk factor for memory loss in aging adults. But it is still unclear exactly how the two issues are related and whether there is potential to slow ...

Report claims success treating Alzheimer's memory loss

October 6, 2014
(HealthDay)— A researcher is reporting success in a small study of reversing memory problems associated with early stage Alzheimer's disease by using a complex program of lifestyle changes, supplements and hormones.

Insulin resistance increases risk for Alzheimer's disease, study finds

July 27, 2015
The fact that obesity increases the risk of cardiovascular disease and some cancers is well known. But a new Iowa State University study adds to the growing evidence that memory loss should also be a top concern.

New biomarker predicts Alzheimer's disease and link to diabetes

December 19, 2016
An enzyme found in the fluid around the brain and spine is giving researchers a snapshot of what happens inside the minds of Alzheimer's patients and how that relates to cognitive decline.

Recommended for you

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

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.