Dementia Overview – Anatomy and current trends and research

Dementia is associated with diseases of the brain, so we will begin by outlining the basic structure and functioning of the human brain and the nervous system. The brain works together with the central and peripheral nervous systems to control the functioning of the human body. The human brain and nervous system are very complex, and new discoveries in neuroscience are being made every day. How the Human Brain Works The brain is often likened to a computer: it processes information it receives from the body and through the senses then sends messages based on the information back to the body through the nervous system, telling the body how to react and behave. These messages are sent as electrical impulses.

For all this to work effectively, the brain needs a good supply of oxygen carried in the blood. This means the vascular system (arteries and veins) must also work effectively. Brain damage can occur if blood supply is decreased or cut off. The brain also allows us to think and experience emotions, which is said to be the root of consciousness and intelligence. The central nervous system consists of the brain and the spinal cord. The peripheral nervous system consists of the nerves that run through the whole body, connecting the brain with all its parts.

Structure of the Human Brain

The brain looks like a walnut, about the size of two clenched fists. It is soft and jelly-like with multiple folds. The brain is a highly complex organ, containing billions of nerve cells and other cells. The cerebrum is divided into the right and left hemispheres, which are connected by the corpus callosum, a thick bundle of nerve fibres. The left hemisphere is responsible for speech and abstract thinking, and the right hemisphere is responsible for spatial thinking and imagery. The right side of the brain controls the left side of the body, and the left side of the brain controls the right side of the body. When the brain experiences damage to one of its sides, the effects are expressed in the opposite side of the body.

How does the brain work?

The brain sends and receives chemical and electrical signals throughout the body. Different signals control different processes, and your brain interprets each. For example, some make you feel tired, while others make you feel pain. Some messages are kept within the brain, while others are relayed through the spine and across the body’s vast network of nerves to distant extremities. The central nervous system relies on billions of neurons (nerve cells) to do this.

Main Parts of the Brain and Their Functions

At a high level, the brain can be divided into the cerebrum, brainstem and cerebellum.

Cerebrum

The cerebrum (front of brain) comprises gray matter (the cerebral cortex) and white matter at its center. The largest part of the brain, the cerebrum initiates and coordinates movement and regulates temperature. Other areas of the cerebrum enable speech, judgment, thinking and reasoning, problem-solving, emotions and learning. Other functions relate to vision, hearing, touch and other senses.

Cerebral Cortex

Cortex is Latin for “bark,” and describes the outer gray matter covering of the cerebrum. The cortex has a large surface area due to its folds, and comprises about half of the brain’s weight. The cerebral cortex is divided into two halves, or hemispheres. It is covered with ridges (gyri) and folds (sulci). The two halves join at a large, deep sulcus (the interhemispheric fissure, AKA the medial longitudinal fissure) that runs from the front of the head to the back. The right hemisphere controls the left side of the body, and the left half controls the right side of the body. The two halves communicate with one another through a large, C-shaped structure of white matter and nerve pathways called the corpus callosum. The corpus callosum is in the center of the cerebrum.

Brainstem

The brainstem (middle of brain) connects the cerebrum with the spinal cord. The brainstem includes the midbrain, the pons and the medulla.

• Midbrain. The midbrain (or mesencephalon) is a very complex structure with a range of different neuron clusters (nuclei and colliculi), neural pathways and other structures. These features facilitate various functions, from hearing and movement to calculating responses and environmental changes. The midbrain also contains the substantia nigra, an area affected by Parkinson’s disease that is rich in dopamine neurons and part of the basal ganglia, which enables movement and coordination.
• Pons. The pons is the origin for four of the 12 cranial nerves, which enable a range of activities such as tear production, chewing, blinking, focusing vision, balance, hearing and facial expression. Named for the Latin word for “bridge,” the pons is the connection between the midbrain and the medulla.
• Medulla. At the bottom of the brainstem, the medulla is where the brain meets the spinal cord. The medulla is essential to survival. Functions of the medulla regulate many bodily activities, including heart rhythm, breathing, blood flow, and oxygen and carbon dioxide levels. The medulla produces reflexive activities such as sneezing, vomiting, coughing and swallowing.

Spinal Cord

The spinal cord extends from the bottom of the medulla and through a large opening in the bottom of the skull. Supported by the vertebrae, the spinal cord carries messages to and from the brain and the rest of the body.

Lobes of the Brain and What They Control

Each brain hemisphere (parts of the cerebrum) has four sections, called lobes: frontal, parietal, temporal and occipital. Each lobe controls specific functions.

• Frontal lobe. The largest lobe of the brain, located in the front of the head, the frontal lobe is involved in personality characteristics, decision-making and movement. Recognition of smell usually involves parts of the frontal lobe. The frontal lobe contains Broca’s area, which is associated with speech ability.
• Parietal lobe. The middle part of the brain, the parietal lobe helps a person identify objects and understand spatial relationships (where one’s body is compared with objects around the person). The parietal lobe is also involved in interpreting pain and touch in the body. The parietal lobe houses Wernicke’s area, which helps the brain understand spoken language.
• Occipital lobe. The occipital lobe is the back part of the brain that is involved with vision.
• Temporal lobe. The sides of the brain, temporal lobes are involved in short-term memory, speech, musical rhythm and some degree of smell recognition.

Deeper Structures Within the Brain that control various functions

Pituitary Gland

Sometimes called the “master gland,” the pituitary gland is a pea-sized structure found deep in the brain behind the bridge of the nose. The pituitary gland governs the function of other glands in the body, regulating the flow of hormones from the thyroid, adrenals, ovaries and testicles. It receives chemical signals from the hypothalamus through its stalk and blood supply.

Hypothalamus

The hypothalamus is located above the pituitary gland and sends it chemical messages that control its function. It regulates body temperature, synchronizes sleep patterns, controls hunger and thirst and also plays a role in some aspects of memory and emotion.

Amygdala

Small, almond-shaped structures, an amygdala is located under each half (hemisphere) of the brain. Included in the limbic system, the amygdalae regulate emotion and memory and are associated with the brain’s reward system, stress, and the “fight or flight” response when someone perceives a threat.

Hippocampus

A curved seahorse-shaped organ on the underside of each temporal lobe, the hippocampus is part of a larger structure called the hippocampal formation. It supports memory, learning, navigation and perception of space. It receives information from the cerebral cortex. The hippocampus is an area of the brain that plays a crucial role in the formation and retrieval of memories, and it is typically one of the first areas of the brain affected by Alzheimer's disease.

Pineal Gland

The pineal gland is located deep in the brain and attached by a stalk to the top of the third ventricle. The pineal gland responds to light and dark and secretes melatonin, which regulates circadian rhythms and the sleep-wake cycle.

How is brain impacted in Dementia

Dementia is a syndrome that affects cognitive abilities and is caused by damage to the brain. In various types of dementia, the brain can be impacted by the buildup of abnormal proteins, reduced blood flow, or other types of damage. As a result, individuals with dementia may experience a range of symptoms, including memory loss, confusion, changes in mood and behavior, and difficulty with daily tasks. Over time, the brain damage becomes more extensive, and symptoms typically worsen. While there is no cure for dementia, early diagnosis and treatment can help manage symptoms and slow its progression.

Resource

You can read more about the brain here Read the following articles to learn more about the brain and nervous system:

• ‘Parts of the Nervous System’ from BrainFacts.org
• ‘The Brain and Nervous System’ from Noba Textbook Series: Psychology

The term ‘dementia’ is an umbrella term that refers to a range of conditions that affect the brain. Dementia is not a normal part of ageing but a symptom of disease. There are many different types of dementia, but they all have an impact on mental, emotional and physical functioning.

Dementia is progressive, which means that functioning continues to decline as time passes.

The following passages illustrate key elements in defining dementia: Dementia is a term used to describe a group of conditions characterised by the gradual impairment of brain function. It is commonly associated with memory loss, but can affect speech, cognition (thought), behaviour and mobility. An individual’s personality may also change, and health and functional ability decline as the condition progresses (Australian Institute of Health and Welfare)

The World Health Organisation describes dementia as a syndrome in which there is ‘deterioration in cognitive function (i.e. the ability to process thought) beyond what might be seen with normal ageing’. It is usually chronic or progressive in its nature and affects memory, thinking, orientation, comprehension, language, and judgement. A decrease in emotional control, social behaviour or motivation can often be seen with the decline in cognitive functioning. (Australian Bureau of Statistics)

Current Research on Dementia

As a worker supporting people living with dementia, you will not need to have in-depth knowledge of current research into dementia from a medical point of view. However, it will be important for you to keep up to date with the latest research so that you can use it to inform the way you treat people living with dementia and provide the best support for your clients and their families.

Some current areas of research in dementia include:

• Brain imaging: Researchers are using advanced brain imaging techniques to better understand the changes that occur in the brain of people with dementia. This can help with earlier diagnosis and treatment, as well as identifying potential targets for drug development.
• Genetics: There is growing evidence that genetic factors play a role in the development of dementia. Researchers are working to identify specific genes that are associated with an increased risk of developing dementia, which can help with early diagnosis and treatment.
• Lifestyle factors: There is growing evidence that certain lifestyle factors, such as diet, exercise, and social engagement, can help reduce the risk of developing dementia. Researchers are studying the effects of lifestyle interventions on cognitive function and brain health.
• Drug development: There are currently no drugs that can cure or slow the progression of dementia, but researchers are working to develop new treatments that can target the underlying causes of the disease.
• Caregiver support: Dementia not only affects the person with the disease but also their caregivers.

Researchers are working to develop interventions that can help support caregivers, such as respite care, counseling, and support groups. Overall, the goal of dementia research is to improve our understanding of this complex disease and develop effective treatments and preventive strategies that can help improve the lives of people with dementia and their families.

Here are some recent research findings on Dementia:

1. Exercise may help prevent or delay dementia A recent study found that regular exercise may help prevent or delay the onset of dementia. The study found that people who engaged in moderate to vigorous exercise had a lower risk of developing dementia compared to those who were sedentary (Gates et al., 2021). Reference: Gates, N. et al. (2021). Exercise for cognitive brain health in aging: A systematic review for an evaluation of dose. Neuropsychology Review, 31, 1-23.
2. Sleep disturbances may increase the risk of dementia A recent study found that people who experience frequent sleep disturbances, such as insomnia, may have an increased risk of developing dementia. The study found that people who reported poor sleep quality had a higher risk of developing dementia compared to those who slept well (Sprecher et al., 2021). Reference: Sprecher, K. E. et al. (2021). Sleep disturbances and risk of dementia in older adults. Sleep, 44(9), zsab101.
3. Social isolation may increase the risk of dementia A recent study found that social isolation may increase the risk of dementia. The study found that people who reported feeling lonely or isolated had a higher risk of developing dementia compared to those who had strong social connections (Mortby et al., 2021). Reference: Mortby, M. E. et al. (2021). Social isolation, loneliness, and dementia risk: A meta-analytic review. Journals of Gerontology: Series B, 76(1), e38-e46.
4. A healthy diet may help prevent or delay dementia A recent study found that a healthy diet, such as the Mediterranean diet, may help prevent or delay the onset of dementia. The study found that people who followed a Mediterranean diet had a lower risk of developing dementia compared to those who did not (Dominguez et al., 2021). Reference: Dominguez, L. J. et al. (2021). Mediterranean diet and cognitive health: A systematic review of the latest evidence. Nutrients, 13(2), 608.

Resource

Visit the following links for information on recent dementia research:

• ‘Dementia Research’ from Dementia Australia
• ‘Dementia Research’ from the Australian Government National Medical Health and Research Council
• ‘Current Research’ from the Australian Alzheimer’s Research Foundation
• ‘7 New Developments in Dementia Research in 2019’ from the Alzheimer’s Society

Watch these two short videos:

‘What Is Dementia?’ by Alzheimer’s Society

‘What Is Dementia?’ by Alzheimer’s Research UK

Then answer the following questions:

Dementia mostly affects older people, although a few conditions that cause dementia also affect younger people. Statistics seem to indicate that dementia is a growing problem. Awareness of dementia and the conditions that cause dementia may be contributing to this perceived increase in numbers. Increasing longevity may also be a factor contributing to the perceived increase in dementia. In the past, many people died before reaching an age where symptoms of dementia typically begin to appear.

According to the World Health Organization (WHO), there are currently an estimated 50 million people worldwide living with dementia, and this number is projected to triple by 2050. In the United States alone, there are currently over 6 million people living with Alzheimer's disease, the most common form of dementia.

Dementia can affect anyone, regardless of gender, ethnicity, or socio-economic status. However, some groups are at higher risk of developing dementia than others. For example, women are more likely than men to develop dementia, and African Americans and Latinos are more likely than Caucasians to develop Alzheimer's disease.

Other risk factors for dementia include a family history of the disease, high blood pressure, diabetes, smoking, and a sedentary lifestyle. However, it is important to note that having one or more of these risk factors does not mean that a person will necessarily develop dementia.

Overall, dementia is a significant public health issue that affects millions of people worldwide. It is important for individuals to take steps to reduce their risk of developing dementia, such as maintaining a healthy lifestyle, engaging in regular physical activity, and seeking early diagnosis and treatment if they are experiencing memory problems or other symptoms of cognitive decline.

According to Dementia Australia (2022),In 2021, there are an estimated 472,000 Australians living with dementia. Without a medical breakthrough, the number of people with dementia is expected to increase to 590,000 by 2028 and 1,076,000 by 2058. Currently, an estimated 250 people are joining the population with dementia each day. The number of new cases of dementia will increase to 318 people per day by 2025 and more than 650 people by 2056. Three in 10 people over the age of 85 and almost one in 10 people over 65 have dementia. In 2021, there were an estimated 28,300 people with younger onset dementia, expected to rise to 29,350 people by 2028 and 41,250 people by 2058.

There are many different types and causes of dementia. The most common types are:

• Alzheimer’s disease
• Vascular Dementia
• Lewy Body Dementia
• Korsakoff’s Syndrome and Alcohol-Related Dementia
• Frontotemporal Dementia
• Huntington’s Disease
• Parkinson’s Disease
• Young-Onset Dementia

Alzheimer’s disease

It is the most common form of dementia, affecting 70% of people with dementia. It is caused by brain cells dying, which in turn causes the brain to shrink. This results in the progressive loss of functioning, and eventual death. It initially affects the hippocampus, which is responsible for memory and learning. As the disease progresses, it can also affect other parts of the brain involved in communication, reasoning, and other cognitive functions. There is no cure, and treatment focuses simply on maintaining the person’s functioning as long as possible and relieving symptoms and side effects, such as agitation, depression and insomnia.

Here is a list of causes and risk of AD:

1. Genetics: Certain genes, such as the APOE gene, have been linked to an increased risk of developing Alzheimer's disease.
2. Age: Alzheimer's disease is most common in people over the age of 65, and the risk increases as people get older.
3. Lifestyle factors: Research suggests that lifestyle factors such as diet, exercise, and social engagement may play a role in the development of Alzheimer's disease. For example, a diet high in saturated fat and cholesterol may increase the risk, while regular physical activity and mental stimulation may decrease the risk.
4. Brain changes: Alzheimer's disease is characterized by the accumulation of beta-amyloid protein plaques and tau protein tangles in the brain, which can interfere with normal brain function and eventually lead to the death of brain cells.
5. Inflammation: Chronic inflammation in the brain has been linked to Alzheimer's disease, and may be caused by factors such as infections, head injuries, or chronic stress.

Resource

Visit the following link to learn about Alzheimer’s in Australia: ‘Alzheimer’s and Dementia in Australia’ from Alzheimer’s Association.

Vascular Dementia

There are several types of vascular dementia, which results from inadequate flow of blood to the brain, often occurring after strokes. High blood pressure and thickening of the arteries are also contributing factors. Multi-infarct dementia, caused by a series of small strokes, develops progressively to cause damage to the brain’s cortex. This is the most common form of vascular dementia. Atherosclerosis, the buildup of plaque in the arteries, a condition known as atherosclerosis, can also increase the risk of VaD. Diabetes is another risk factor for VaD, as it can lead to damage to the blood vessels in the brain and other organs. Smoking has been linked to an increased risk of VaD, as it can damage the blood vessels throughout the body. The progress of the disease is similar to that of Alzheimer’s and may include mood swings, severe depression and epileptic seizures. Subcortical vascular dementia is also relatively common and related to changes in the brain resulting from a stroke. Brain damage that has already occurred cannot be reversed, but treatment to prevent future strokes through healthy lifestyle as well as drugs to reduce cholesterol and high blood pressure can prevent further damage.

Resource

Learn more about vascular dementia at the following link: ‘Vascular Dementia’ from Dementia Australia.

Lewy Body Dementia

Lewy bodies are abnormal, round structures that develop inside nerve cells in the brain and result in dementia. Lewy body disease is similar to Alzheimer’s and Parkinson’s, and there is no known cause or cure. The progress of Lewy body disease can be rapid. Symptoms can include hallucinations, fluctuations in mental state, stiffness and physical tremors. Treatment focuses on the use of drugs to relieve symptoms.

Some of the causes of LBD include:

1. Genetics: LBD can sometimes run in families, and some genetic mutations have been linked to an increased risk of developing the condition.
2. Age: Lewy body dementia is more common in people over the age of 60, although it can occur in younger people as well.
3. Environmental factors: Exposure to certain toxins or chemicals may increase the risk of developing LBD.
4. Other medical conditions: People with certain medical conditions, such as Parkinson's disease or REM sleep behavior disorder, may have a higher risk of developing LBD.
5. Brain injuries: Traumatic brain injuries have been associated with an increased risk of developing LBD.
6. Imbalances in brain chemicals: Imbalances in certain brain chemicals, such as dopamine, acetylcholine, and serotonin, may play a role in the development of LBD.

‘Lewy Body Disease - Robin and Lis’ by Dementia Australia

Learn more about Lewy body disease by watching the following video:

Korsakoff’s Syndrome and Alcohol-Related Dementia

Excessive intake of alcohol over a long period of time damages the brain and can result in the person developing alcohol-related dementia and/or Korsakoff’s syndrome (also known as Wernicke-Korsakoff syndrome), which is one of the forms of dementia that affects younger people.

Its causes include:

1. Direct toxic effects of alcohol on the brain: Long-term heavy alcohol use can cause damage to the brain cells, leading to cognitive impairment and memory loss.
2. Nutritional deficiencies: Alcohol can interfere with the absorption of certain vitamins and minerals, such as thiamine, which is essential for brain function. Chronic alcohol use can lead to malnutrition and thiamine deficiency, which can contribute to the development of dementia.
3. Liver disease: Long-term heavy alcohol use can cause liver damage and impair its ability to remove toxins from the body, leading to further damage to the brain.
4. Cardiovascular disease: Chronic heavy alcohol use can increase the risk of cardiovascular disease, which can lead to reduced blood flow to the brain and contribute to the development of dementia.
5. Other lifestyle factors: Individuals who abuse alcohol may also have other unhealthy lifestyle factors, such as poor diet and lack of exercise, which can further increase their risk of developing dementia.

‘2-Minute Neuroscience, Alcohol’ by Neuroscientifically Challenged 

The following video details the effects of alcohol on the brain:

Frontotemporal Dementia

Frontotemporal dementia (FTD) is caused by damage to the frontal and/or temporal lobes of the brain, which govern self-control, mood, social skills, attention, planning and judgement. FTD results in changes to thought processes, emotions and personality.

Here are some of the known causes and risk factors for FTD:

1. Genetic factors: Some cases of FTD are caused by mutations in certain genes, such as the MAPT, GRN, and C9orf72 genes. These mutations can lead to the abnormal accumulation of proteins in the brain, which can cause damage to the brain cells and lead to the development of FTD.
2. Environmental factors: There is some evidence to suggest that exposure to certain environmental toxins, such as pesticides, may increase the risk of developing FTD.
3. Age: FTD typically occurs in individuals between the ages of 45 and 65, although it can occur at any age.
4. Gender: FTD appears to be slightly more common in men than in women.
5. Family history: Individuals with a family history of FTD or other neurodegenerative disorders may be at increased risk of developing the disease.
6. Brain injury: There is some evidence to suggest that a history of traumatic brain injury may increase the risk of developing FTD.
7. Neuroinflammation: Inflammation in the brain, which can be caused by a variety of factors, may contribute to the development and progression of FTD.

Symptoms can appear when a person is in their fifties or sixties, including personality changes and the loss of language skills. There is a genetic component in about 10–15% of cases, but this is not yet properly understood.

‘Frontotemporal Dementia’ by MassGeneralHospital

Learn more about frontotemporal dementia by watching the following video:

Huntington’s Disease

Huntington’s disease is a progressive disease that often results in premature death, but it can take between 10 and 30 years to progress to a fatal state. It is characterised by uncontrollable, jerky body movements (known as chorea), which can resemble dancing. It is a brain disease that affects the nervous system. Other symptoms include apraxia, which means that the person is unable to perform familiar movements; deterioration in memory, cognitive processes, judgment and the ability to plan and organise; and the loss of control over bodily functions. Huntington’s disease is genetically transmitted. Children of an affected parent have a 50% chance of inheriting the gene, developing the disease and/or transmitting it to their own children. It can appear at any age, but most commonly presents symptoms in a person’s forties and fifties. It is thought that the related gene interferes with the body’s ability to manufacture a protein that is essential for normal brain development. There is no cure or treatment to stop or reverse the progress of Huntington’s disease. Other common causes include:

1. Toxic effects of the mutant protein: The mutant huntingtin protein can accumulate in the brain cells, disrupting their normal function and leading to their degeneration and death.
2. Interference with normal cellular processes: The mutant protein can interfere with the normal cellular processes, such as regulating gene expression and transporting proteins within the cells.
3. Neuroinflammation: The accumulation of the mutant protein can trigger an inflammatory response in the brain, leading to further damage and cell death.
4. Genetic and environmental factors: While a genetic mutation causes HD, there is evidence that environmental factors may also play a role in the development and progression of the disease.

‘2-Minute Neuroscience: Huntington’s Disease’ by Neuroscientifically Challenged

The following video teaches about Huntington’s disease:

Parkinson’s Disease

Parkinson’s disease is a neurological condition that affects movement and balance. It occurs in about one to two people in a thousand, increasing to one in a hundred in people over the age of 60. Research shows Parkinson’s disease causes the death of nerve cells that produce dopamine in the brain, which results in difficulty controlling muscle tension and movement, which then leads to muscle tremors, rigid limbs, loss of balance and difficulty walking.

Clear causes have not yet been identified but may include:

1. Genetic factors: Although most cases of Parkinson's disease are not inherited, there are some genetic mutations that can increase the risk of developing the disease. For example, mutations in the LRRK2, SNCA, and Parkin genes are known to be associated with increased risk of PD.
2. Environmental factors: Exposure to certain toxins, such as pesticides and herbicides, has been linked to an increased risk of developing Parkinson's disease. It has also been suggested that head injuries, particularly those that involve loss of consciousness, may increase the risk of PD.
3. Age: Parkinson's disease is more common in older adults, with the risk increasing significantly after the age of 60.
4. Gender: Parkinson's disease appears to be slightly more common in men than in women.
5. Family history: Individuals with a family history of Parkinson's disease may be at increased risk of developing the disease. Neuroinflammation: Inflammation in the brain may contribute to the development and progression of Parkinson's disease.

‘2-Minute Neuroscience: Parkinson’s Disease’ by Neuroscientifically Challenged

Learn more about Parkinson’s disease by watching the following video:

Young-Onset Dementia

Young-onset dementia is any form of dementia that occurs in a person under the age of 65. Dementia can occur in a person as young as 30 and is most commonly the result of Alzheimer’s disease, vascular dementia or frontotemporal dementia.

Some causes of this dementia type include:

1. Infections: Certain infections, such as HIV/AIDS, can cause damage to the brain that may lead to the development of dementia.
2. Substance abuse: Long-term alcohol or drug abuse can damage the brain and increase the risk of developing dementia.
3. Cardiovascular disease: Cardiovascular disease, including high blood pressure, high cholesterol, and diabetes, can increase the risk of developing dementia.
4. Environmental factors: Chronic stress, Exposure to environmental toxins, such as lead, can increase the risk of developing dementia.
5. Lifestyle factors: Unhealthy lifestyle factors, such as a poor diet, lack of exercise, and smoking, can increase the risk of developing dementia.

The impact of dementia in a relatively early stage of life can be traumatic and can have economic and social implications different to those caused by dementia in a later stage of life. Progressive disease and symptoms vary according to the type of dementia but can include memory loss and difficulties with thought processes, communication and functioning within the home or community. Management of the disease also varies.

‘Living With Young-Onset Dementia’ by Financial Times

Watch the following video to learn how young-onset dementia can affect a person’s life:

Many molecular and cellular changes take place in the brain of a person with Alzheimer’s disease. These changes can be observed in brain tissue under the microscope after death. Investigations are underway to determine which changes may cause Alzheimer’s and which may be a result of the disease.

Amyloid Plaques

The beta-amyloid protein involved in Alzheimer’s comes in several different molecular forms that collect between neurons. It is formed from the breakdown of a larger protein, called amyloid precursor protein. One form, beta-amyloid 42, is thought to be especially toxic. In the Alzheimer’s brain, abnormal levels of this naturally occurring protein clump together to form plaques that collect between neurons and disrupt cell function. Research is ongoing to better understand how, and at what stage of the disease, the various forms of beta-amyloid influence Alzheimer’s.

Neurofibrillary Tangles

Neurofibrillary tangles are abnormal accumulations of a protein called tau that collect inside neurons. Healthy neurons, in part, are supported internally by structures called microtubules, which help guide nutrients and molecules from the cell body to the axon and dendrites. In healthy neurons, tau normally binds to and stabilizes microtubules. In Alzheimer’s disease, however, abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. These tangles block the neuron’s transport system, which harms the synaptic communication between neurons. Emerging evidence suggests that Alzheimer’s-related brain changes may result from a complex interplay among abnormal tau and beta-amyloid proteins and several other factors. It appears that abnormal tau accumulates in specific brain regions involved in memory. Beta-amyloid clumps into plaques between neurons. As the level of beta-amyloid reaches a tipping point, there is a rapid spread of tau throughout the brain.

Chronic Inflammation

Research suggests that the buildup of glial cells may cause chronic inflammation normally meant to help keep the brain free of debris. One type of glial cell, microglia, engulfs and destroys waste and toxins in a healthy brain. In Alzheimer’s, microglia fail to clear away waste, debris, and protein collections, including beta-amyloid plaques. Researchers are trying to discover why microglia fails to perform this vital function in Alzheimer’s. One focus of study is a gene called TREM2. Normally, TREM2 tells the microglia cells to clear beta-amyloid plaques from the brain and helps fight inflammation in the brain. In the brains of people where this gene does not function normally, plaques build up between neurons. Astrocytes—another type of glial cell—are signaled to help clear the buildup of plaques and other cellular debris left behind. These microglia and astrocytes collect around the neurons but fail to perform their debris-clearing function. In addition, they release chemicals that cause chronic inflammation and further damage the neurons they are meant to protect.

Loss of Neuronal Connections and Cell Death

In Alzheimer’s disease, as neurons are injured and die throughout the brain, connections between networks of neurons may break down, and many brain regions begin to shrink. By the final stages of Alzheimer’s, this process—called brain atrophy—is widespread, causing significant loss of brain volume.

We have reached the end of the topic Now it's your turn to try the quiz to test your knowledge for this topic!