Monthly Archives: januar 2017

Researchers have found a potentially promising treatment for Alzheimer’s disease, by noticing a similarity in the way insulin signaling works in the brain and in the pancreas of diabetic patients.

«In the pancreas, the Kir6.2 channel blockade increases the insulin signaling, and insulin signaling decreases the blood glucose levels,» says Dr. Shigeki Moriguchi, one of the authors of the paper. «In the brain, insulin signaling increases the acquisition of memory through CaM kinase II activation by Kir6.2 channel blockade.»

The research group concluded that Alzheimer’s disease can be described as a ‘diabetic disorder’ of the brain.

Memantine, a drug widely used to treat Alzheimer’s disease, is a well-known inhibitor of the N-methyl-D-aspartate (NMDA) receptors that prevent excessive glutamate transmission in the brain. Researchers have now found that memantine also inhibits the ATP-sensitive potassium channel (Kir6.2 channel), improving insulin signal dysfunction in the brain.

In their experiment with mice, the researchers found that memantine treatment improved impaired hippocampal long-term potentiation (LTP) and memory-related behaviors in the mice through the inhibition of KATP channel Kir6.2.

The researchers say they hope the results of their study and the parallels drawn with diabetes will lead to new treatments for Alzheimer’s disease using the inhibition of Kir6.2 channel.

Paper: “Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer’s disease therapy”
Reprinted from materials provided by Tohoku University.

New research reveals that foods like fruits and vegetables that are high in antioxidant nutrients and carotenoids are associated with better function in amyotrophic lateral sclerosis (ALS) patients around the time of diagnosis. This is among the first studies to evaluate diet in association with ALS function and the first to show that healthy nutrients and antioxidants are associated with better ALS functioning. The findings are published in JAMA Neurology.

Researchers examined the links between nutritional intake and severity of ALS for patients who had ALS symptoms for 18 months or less. The study, which relied on nutrient intake reported using a food questionnaire, followed 302 participants recruited at 16 clinical centers throughout the U.S. The researchers used a validated measure of ALS severity and respiratory function.

The researchers found that “nutrition plays a role both in triggering the disease and why it progresses.” They also found that milk and lunch meats were associated with lower measures of function, or more severe disease. Two different statistical analyses both indicate that diet may help minimize the severity of ALS and point to the role of oxidative stress in ALS severity.
Paper: “Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis”
Reprinted from materials provided by: Columbia University

A collaboration of 32 researchers in seven countries has found a genetic mutation they say confers a risk for development of Parkinson’s disease earlier than usual.

The study, published in Brain, is important because the risk comes from a single mutation in the PTEN-induced putative kinase 1 (PINK1) gene. Investigators had believed that this rare form of Parkinson’s developed only when a person inherited mutations in both PINK1 alleles (one from each parent).

PINK1 works with another gene, PARKIN, to ensure that mitochondria in neurons remain healthy. When functioning, proteins from both genes work together to ensure the safe disposal of damaged mitochondria from the cell. Mutations in both PINK1 alleles (or copies) or in both PARKIN alleles mean that the PINK1-PARKIN pathway cannot function, and damaged mitochondria accumulate in a neuron, leading to its death.

This study showed that a specific mutation (p.G411S) in one copy of PINK1 substantially impairs this same pathway by inhibiting the protein produced from other healthy PINK1 allele.

Paper: “Heterozygous PINK1 p.G411S increases risk of Parkinson’s disease via a dominant-negative mechanism”

Reprinted from materials provided by the Mayo Clinic.

A lack of shrinkage in the area of the brain responsible for memory may be a sign that people with thinking and memory problems may go on to develop dementia with Lewy bodies rather than Alzheimer’s disease, according to a new study published in Neurology.

Shrinkage in this hippocampus area of the brain is an early sign of Alzheimer’s disease. Dementia with Lewy bodies is a common form of dementia. Because it has many symptoms in common with Alzheimer’s and Parkinson’s disease, it can be difficult to diagnose. It can include movement problems, sleep disorders and hallucinations.

For the study, 160 people with thinking and memory problems, called mild cognitive impairment, had brain MRI scans at the start of the study to measure the size of the hippocampus. They also had yearly tests for an average of two years. During that time, 61 people, or 38 percent, developed Alzheimer’s disease and 20 people, or 13 percent, progressed to probable dementia with Lewy bodies. It is called probable dementia with Lewy bodies because the disease can be diagnosed definitively only by an autopsy after death. The people who had no shrinkage in the hippocampus were 5.8 times more likely to develop probable dementia with Lewy bodies than those who had hippocampal shrinkage. A total of 17 out of the 20, or 85 percent, of people who developed dementia with Lewy bodies had a normal hippocampus volume; while 37 of the 61, or 61 percent, of people who developed Alzheimer’s disease had shrinkage in the hippocampus.

The relationship was even stronger when researchers looked only at people whose thinking problems did not include memory issues. Dementia with Lewy bodies does not always affect memory; thinking skills that are affected usually include attention, problem solving, and the ability to interpret visual information.

Paper: “Hippocampal volumes predict risk of dementia with Lewy bodies in mild cognitive impairment”
Reprinted from materials provided by AAN.

An international collaboration has shed light on the basal forebrain region, where the degeneration of neural tissue caused by Alzheimer’s disease appears even before cognitive and behavioral symptoms of the disease emerge.

The research, published in Nature Communications, used data obtained from the Alzheimer’s Disease Neuroimaging Initiative database.

The basal forebrain contains very large and densely connected neurons that are particularly vulnerable to the disease. The researchers show that, as Alzheimer’s progresses, degeneration of the basal forebrain predicts subsequent degeneration in temporal lobe areas of the brain involved in memory. This pattern is consistent with other research showing that Alzheimer’s indeed spreads across brain regions over time, but the study challenges a widely held belief that the disease originates in the temporal lobe.

In the two-year study, the researchers were able to determine that individuals with MCI or Alzheimer’s disease showed greater losses in gray matter volume in both the basal forebrain and temporal lobe, compared with cognitively normal controls. Intriguingly, they showed that over the two-year period, degeneration of neural tissue in the basal forebrain predicted subsequent tissue degeneration in the temporal lobe, but not the other way around.

A sampling of spinal fluid from healthy adults can detect an abnormal level of beta amyloid, indicative of Alzheimer’s. Test results showed that temporal lobes looked the same regardless of amyloid level, but the basal forebrain showed notable degeneration among those seemingly healthy adults with abnormal amyloid levels.

Paper: “Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer’s pathology”
Reprinted from materials provided by Cornell University.