Yearly Archives: 2017

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.

A Japanese research team has found that collapse of the Mitochondria-Associated Membrane (MAM) is a common pathological hallmark to two distinct inherited forms of ALS: SOD1- and SIGMAR1-linked ALS. The research findings were reported in EMBO Molecular Medicine.

Recent studies have revealed that the MAM plays a key role in cellular homeostasis, such as lipid synthesis, protein degradation, and energy metabolism. Intriguingly, a recessive mutation in SIGMAR1 gene, which encodes sigma 1 receptor (Sig1R), a chaperone enriched in the MAM, is causative for a juvenile ALS. In this study, the researchers identified a novel ALS-linked SIGMAR1 mutation, c.283dupC/p.L95fs in a juvenile-onset ALS case. Moreover, ALS-linked Sig1R mutant proteins were unstable and non-functional, indicating a loss-of function mechanism in SIGMAR1-linked ALS.

A loss of Sig1R function induced MAM disruption in neurons. However, it was still unknown whether the MAM alternation was also involved in the other ALS cases. To address this question, the researchers cross-bred SIGMAR1 deficient mice with the other inherited ALS mice which overexpress a mutant form of SOD1 gene. SIGMAR1 deficiency accelerated disease onset of SOD1-ALS mice by more than 20%. In those mice, inositol triphosphate receptor type-3 (IP3R3), a MAM-enriched calcium ion (Ca2+) channel, was disappeared from the MAM. The loss of proper localization of IP3R3 led to Ca2++ dysregulation to exacerbate the neurodegeneration. The researchers also found that IP3R3 was selectively enriched in motor neurons, suggesting that integrity of the MAM is crucial for the selective vulnerability in ALS.

These results provide new perspectives regarding future therapeutics, especially focused on preventing the MAM disruption for ALS patients. Together with the research from other groups, collapse of the MAM is widely observed in the other genetic causes of ALS, and therefore it may be applicable to sporadic ALS patients.

Paper: “Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS”
Reprinted from materials provided by Nagoya University.