The use of proton pump inhibitors does not increase the risk of Alzheimer’s disease, according to a recent study. Proton pump inhibitors are a type of antiulcer drug that is commonly used among older people.
For the first time, researchers have demonstrated a surprising effect of microglia, the scavenger cells of the brain: If these cells lack the TDP-43 protein, they not only remove Alzheimer’s plaques, but also synapses. This removal of synapses by these cells presumably lead to neurodegeneration observed in Alzheimer’s and other neurodegenerative diseases.
Similar to other neurodegenerative disorders, Alzheimer’s is a disease in which the cognitive abilities of afflicted persons continuously worsen. The reason is the increasing loss of synapses, the contact points of the neurons, in the brain. In the case of Alzheimer’s, certain protein fragments, the β-amyloid peptides, are suspected of causing the death of neurons. These protein fragments clump together and form the disease’s characteristic plaques.
Voracious microglia cells destroy brain synapses
Together with researchers from Great Britain and the United States, the group of Lawrence Rajendran from the Institute for Regenerative Medicine of the University of Zurich now shows that dysfunctional microglia cells contribute to the loss of synapses in Alzheimer’s and other neurodegenerative diseases. These scavenger cells usually monitor the function of neurons in the brain by removing excess synapses during development or toxic protein aggregates. Until now, their role in neurodegenerative disorders remains controversial.
In an initial step, the researchers looked at the effect that certain risk genes for Alzheimer’s have on the production of the β-amyloid peptide. They found no effect in neurons. This led the researchers then to examine the function of these risk genes in microglia cells — and made a discovery: If they turned off the gene for the TDP-43 protein in these scavenger cells, these cells remove β-amyloid very efficiently. This is due to the fact that the lack of TDP-43 protein in microglia led to an increased scavenging activity, called phagocytosis.
The TDP-43 protein regulates the activity of scavenger cells
In the next step, researchers used mice, which acted as a disease model for Alzheimer’s. In this case, as well, they switched off TDP-43 in microglia and observed once more that the cells efficiently eliminated the β-amyloid. Surprisingly, the increased scavenging activity of microglia in mice led also to a significant loss of synapses at the same time. This synapse loss occurred even in mice that do not produce human amyloid. This finding that increased phagocytosis of microglia can induce synapse loss led researchers to hypothesize that perhaps, during aging, dysfunctional microglia could display aberrant phagocytic activity. “Nutrient deprivation or starvation-like mechanism during aging could enhance phagocytic mechanism in microglia and this could lead to synaptic loss” Lawrence Rajendran assumes.
Direct role in neurodegeneration
The results show that the role of microglia cells in neurodegenerative diseases like Alzheimer’s has been underestimated. It is not limited to influencing the course of the disease through inflammatory reactions and the release of neurotoxic molecules as previously assumed. Instead, this study shows that they can actively induce neurodegeneration. “Dysfunction of the microglia cells may be an important reason why many Alzheimer’s medications reduce the amyloid plaques in clinical testing, but the cognitive functions in patients do not lead to improvement,” Rajendran says.
Materials provided by University of Zurich. Note: Content may be edited for style and length.
Society for Neuroscience. “Alzheimer’s gene associated with failure to adapt to cognitive challenge in healthy adults.” ScienceDaily. ScienceDaily, 26 June 2017. <www.sciencedaily.com/releases/2017/06/170626131756.htm>.
Society for Neuroscience. (2017, June 26). Alzheimer’s gene associated with failure to adapt to cognitive challenge in healthy adults. ScienceDaily. Retrieved June 28, 2017 from www.sciencedaily.com/releases/2017/06/170626131756.htm
Society for Neuroscience. “Alzheimer’s gene associated with failure to adapt to cognitive challenge in healthy adults.” ScienceDaily. www.sciencedaily.com/releases/2017/06/170626131756.htm (accessed June 28, 2017).
Going for a walk outside, reading, listening to music — these and other enjoyable activities can reduce blood pressure for elderly caregivers of spouses with Alzheimer’s disease, suggests a study in Psychosomatic Medicine: Journal of Biobehavioral Medicine, the official journal of the American Psychosomatic Society. The journal is published by Wolters Kluwer.
“Greater engagement in pleasant leisure activities was associated with lowered caregivers’ blood pressure over time,” according to the report by Brent T. Mausbach, PhD, of University of California San Diego and colleagues. “Participation in pleasant leisure activities may have cardiovascular benefits for Alzheimer’s caregivers.”
The study included 126 caregivers enrolled in the UCSD Alzheimer’s Caregiver Study, a follow-up study evaluating associations between stress, coping, and cardiovascular risk in Alzheimer’s caregivers. The caregivers were 89 women and 37 men, average age 74 years, providing in-home care for a spouse with Alzheimer’s disease.
As part of annual interviews over five years, the caregivers provided information on how often they engaged in various pleasant leisure activities. These ratings were analyzed for association with blood pressure over time, with adjustment for demographic and health factors.
The caregivers reported high levels of enjoyable activities — most said they spent time outdoors, laughing, watching TV, listening to music, and reading or listening to stories. About half of caregivers said they exercised frequently.
Caregivers who more frequently engaged in pleasant leisure activities had lower mean arterial blood pressure (a measure of average blood pressure). In follow-up analyses, these activities were associated with a significant reduction in diastolic pressure (the second, lower blood pressure number), although not in systolic pressure (the first, higher number).
As expected, caregivers who exercised more frequently had lower blood pressure. However, other types of “more sedentary, reflective” activities also led to reduced blood pressure. These included reading, listening to music, shopping, and recalling past events.
Blood pressure also decreased after nursing home placement or death of the person with Alzheimer’s disease. That was consistent with previous studies showing that caregivers’ health improves after their caregiving duties end.
Being a caregiver for a disabled loved one is a highly stressful experience, associated with an increased risk of cardiovascular disease and death. Stress may contribute to high blood pressure, which is the strongest risk factor for cardiovascular disease. The new results suggest that leisure activities are a behavioral factor that can prevent the development of high blood pressure in Alzheimer’s caregivers.
Dr. Mausbach notes that the study assessed both the frequency and enjoyment of activities. The premise is that rather than recommending certain activities to everyone, it’s important for caregivers to enjoy the activities they do to receive benefit. While the study can’t determine how many activities people should do, “We believe three to four enjoyed activities each week could have a modest impact on an individual’s blood pressure,” Dr. Mausbach commented. “From there, the more an individual can do, the better the impact.”
The researchers have been conducting a clinical trial to examine the effect of a therapy to increase pleasant leisure activities. “We recognize caregivers may have a difficult time engaging in pleasant leisure activities because they are busy with their caregiving duties,” said Dr. Mausbach. “So we work with caregivers to find activities they can more confidently engage in even when their spouse is present. We also help them monitor their use of time so they know the times during the day when they are most capable of doing activities. Further, if caregivers use respite services, they are in a perfect position to use some of their respite time to engage in these activities.”