Find all causes of Alzheimer's disease and a cure

CELL has published the results of a collaboration between Rudy Tanzi, PH.D. and Huda Zoghbi, M.D. The work shows that a rare gene associated with an increased risk of Alzheimer’s, ATXN1, regulates an increase in BACE1, an enzyme that contributes to amyloid plaque accumulation.

Neurodegenerative disorders tend to fall into two distinct categories that are not thought of as overlapping: those that affect movement, called ataxias, and those that affect mental functioning, called dementias. ATXN1 is a rare Alzheimer’s associated gene that has been extensively studied in spinocerebellar ataxia type1 (SCA1), a neurodegenerative disorder.  SCA1 has no known effective treatment or cure and can affect anyone at any age. In many cases, people are not aware that they carry a relevant gene until after they have children. An estimated 150,000 people are living with spinocerebellar ataxia in the United States and the average age of onset is in the forties. SCA1 symptomsvinclude the deterioration of motor coordination, balance, and progressive difficulty in swallowing and breathing in late stages. Impairments in verbal memory and frontal executive dysfunction also occur in later stages of the disease.

ATXN1 is a rare Alzheimer’s associated gene that has been studied in the neurodegenerative disorder, spinocerebellar ataxia type 1. Those who suffer from this disorder experience Alzheimer’s like dementia later in the progression of the disease. To test the hypothesis that ATXN1 might be involved in Alzheimer’s disease, the researchers used mice that were genetically modified to have the ATXN1 gene knocked out. The researchers were interested in determining whether the loss of ATXN1 would lead to biochemical changes that resembled the changes observed in the brain during Alzheimer’s disease. BACE1, the b-secretase enzyme that cleaves amyloid precursor protein and generates amyloid plaques, was increased by 45% in the ATXN1 knockout mice. These mice display impairments in learning in the hippocampus. This paper provides evidence that ATXN1 plays a role in learning and memory.

Prior to this study, there has been no evidence that any known candidate genes for Alzheimer’s disease could regulate BACE1 expression in the brain.

This paper is groundbreaking for its ability to demonstrate a unique regulatory mechanism by which ATXN1, a gene more commonly associated with motor neurodegeneration, can affect BACE1 levels. An increase in BACE1 expression can decrease neural precursor cell proliferation and negatively impact learning, memory, and the birth of new neurons. An interesting next direction for the field will be to determine how altering levels of amyloid precursor protein or BACE1 influences adult hippocampal neurogenesis – a process that is known to go awry in Alzheimer’s.

Links:

• https://www.eurekalert.org/pub_releases/2019-08/mgh-glt082019.php

There are 50 million people worldwide with Alzheimer’s disease, and while much remains mysterious about Alzheimer’s, progress is being made. Many of our researchers are investigating lifestyle activities and interventions to determine which would assist with keeping our brains as healthy as possible for as long as possible.

Dr. Rudy Tanzi of Harvard Medical School, the Chair of the Cure Alzheimer’s Fund Research Leadership Group, says we know more than you might think about how to keep our brains healthy. The good news is that there are proven ways to reduce the inflammation in the brain that is a hallmark of Alzheimer’s disease, and he refers to six steps everyone can take as a SHIELD for their brain.

SLEEP

The impact of sleep on Alzheimer’s disease development has been studied extensively. During sleep, your brain has a natural system for clearing out the debris that builds up and can be destructive, including amyloid beta plaque and tau. When there is too much plaque in the brain, cell function may be compromised and the plaque can bind to nerve cells, harming them over time. Lack of sleep interferes with the brain’s ability to clear the debris. Aim for at least eight hours of sleep each night to ensure your brain has the chance to carry out this cleanup process. “If you are not able to get eight hours of continuous sleep, take naps,” Dr. Tanzi says.

HANDLE STRESS

Studies show that stress affects how the brain functions. Excessive levels of stress can cause and exacerbate disease, in large part through the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis which elevates cortisol levels. High levels of blood cortisol have a negative impact on memory and can increase levels of inflammation. There is evidence that ongoing, chronic stress may rewire the brain. It is important to find ways to reduce stress. Incorporating relaxation techniques such as meditation into our daily lives can help with overall stress management.

INTERACT

A six-year study published in 2013 with adults older than 65 who had not yet shown cognitive impairment found that those with higher levels of social interaction were less likely to develop dementia. Since this study was finalized, numerous other studies have shown that social interaction preserves cognitive function, as well as a strong connection between loneliness and impaired cognitive function. Numerous studies confirm that older adults with dementia who have a strong social network experience delayed cognitive function. There are many benefits to staying socially active by engaging with friends and family and meeting new people. These include a protective influence on the comprehension and reasoning ability as well as a lower risk of developing symptoms of memory loss. An active social life can open up a new world of opportunity and provide motivation to introduce healthy habits into your life.

EXERCISE

Exercise has been shown to create biochemical changes in the brain related to the health of our nerve cells. In short, exercise facilitates the creation of new nerves and synapses, referred to as neurogenesis, in the hippocampus of the brain. The hippocampus is crucial for memory retrieval and the formation of new memories. Research has found that one of the first areas in the brain affected by Alzheimer’s disease is the hippocampus. Exercise helps prevent atrophy in this area of the brain. The recommendation is to move more: whatever your current level of exercise, just move a little more. Even if you are sedentary, begin by taking a short walk, and increase the length of your walks over time.

LEARN NEW THINGS

In addition to physical exercise, mental exercise is a factor in delaying cognitive decline. Learning new things as we age can keep us mentally sharp and builds our neural networks. For example, reading books, learning a new language or new field of knowledge, practicing memorizing lists or engaging in a new hobby helps keep the brain stimulated. The more challenging and complex, the greater the benefit. “The more synapses you make, the more you can lose before you lose it,” Tanzi says.

DIET

The Mediterranean diet has been shown to benefit your brain the most. That diet emphasizes eating more fruits and vegetables, nuts, olive oil and fish, and reducing consumption of red meat. “The Mediterranean dietis best for your brain,” says Tanzi, adding that your diet has an effect on your microbiome and neuroinflammation.

Dr. Tanzi stresses that making small changes every day can help the health of your brain. “And,” he points out, “these are all things you can do now.”