Amyloid Hypothesis Versus Tau Hypothesis
A central but controversial issue in the pathogenesis of AD is the relationship between amyloid deposition and NFT formation. Evidence shows that abnormal amyloid metabolism plays a key pathogenic role. At high concentrations, the fibrillar form of Ab has been shown to be neurotoxic to cultured neurons.
Cultured cortical and hippocampal neurons treated with Ab protein exhibit changes characteristic of apoptosis , including nuclear chromatin condensation, plasma membrane blebbing, and internucleosomal DNA fragmentation. The fibrillar form of Ab has also been shown to alter the phosphorylation state of tau protein.
The identification of several point mutations within the APP gene in some patients with early-onset familial AD and the development of transgenic mice exhibiting cognitive changes and SPs also incriminate Ab in AD. The apolipoprotein E E4 allele, which has been linked with significantly increased risk for developing AD, may promote inability to suppress production of amyloid, increased production of amyloid, or impaired clearance of amyloid with collection outside of the neuron.
Autopsies have shown that patients with 1 or 2 copies of the APOE E4 allele tend to have more amyloid. Additional evidence comes from recent experimental data supporting the role of presenilins in Ab metabolism, as well as findings of abnormal production of Ab protein in presenilin-mutation familial Alzheimer disease.
What Does Alzheimers Disease Look Like
Memory problems are typically one of the first signs of Alzheimers, though initial symptoms may vary from person to person. A decline in other aspects of thinking, such as finding the right words, vision/spatial issues, and impaired reasoning or judgment, may also signal the very early stages of Alzheimers disease. Mild cognitive impairment is a condition that can be an early sign of Alzheimers, but not everyone with MCI will develop the disease.
People with Alzheimers have trouble doing everyday things like driving a car, cooking a meal, or paying bills. They may ask the same questions over and over, get lost easily, lose things or put them in odd places, and find even simple things confusing. As the disease progresses, some people become worried, angry, or violent.
What Is Known About Alzheimers Disease
Scientists do not yet fully understand what causes Alzheimers disease. There likely is not a single cause but rather several factors that can affect each person differently.
- Age is the best known risk factor for Alzheimers disease.
- Family historyresearchers believe that genetics may play a role in developing Alzheimers disease. However, genes do not equal destiny. A healthy lifestyle may help reduce your risk of developing Alzheimers disease. Two large, long term studies indicate that adequate physical activity, a nutritious diet, limited alcohol consumption, and not smoking may help people. To learn more about the study, you can listen to a short podcast.
- Changes in the brain can begin years before the first symptoms appear.
- Researchers are studying whether education, diet, and environment play a role in developing Alzheimers disease.
- There is growing scientific evidence that healthy behaviors, which have been shown to prevent cancer, diabetes, and heart disease, may also reduce risk for subjective cognitive decline. Heres 8 ways.
Also Check: Can Schizophrenia Lead To Dementia
Hammer Of The Witches
In the Middle Ages, mental illnesses such as depression or dementia were regarded as a kind of punishment necessarily imposed by God for sins comitted. As the reason for dementia was not elucidated rationally in this period, it was considered that abnormal activities and mental symptoms generated in the dementia patients were due to demon-possession, and thus naturally subject to hatred. Patients with dementia were representative victims of a witch hunt that was widespread over the 14th to 15th centuries.
In 1486, Malleus Maleficarum was published by Heinrich Kramer and Jacob Sprenger who were priests of the Dominican order in the Roman Catholic Church. This book contained the criteria to identify witches, instructions and methods for trial and execution of a sentence, as a textbook of a witch hunt approved by Pope Innocent VIII. It was revised dozens of times and spread throughout the world in various languages. Hundreds of thousands have been burned dreadfully at the stake since the book was published.
People designated as witches according to the criteria defined in the Hammer of the Witches, were mainly mental patients, and most of them were women with symptoms such as paranoia, mania, schizophrenia, epilepsy and senile dementia. For no other reason than their mental instability, they became victims of a witch hunt and a great number of people across Europe were burned to ashes on the rack.
The Quest For Prevention
As time and my own understanding progress, I think that we should be looking for a way to prevent Alzheimers disease rather than a way to cure it once it has been diagnosed. In the 100+ years since Dr. Alzheimer first described the disease, very little progress has been made toward this end, whether cure or prevention. On the other hand, our understanding of the brain has advanced markedly in the last few years. This gives me some hope that we will soon discover a way to prevent neurological diseases like Alzheimers.
You May Like: How To Prevent Alzheimer’s And Parkinson’s
Lost Time An Ethical Challenge For The Present And The Future With A Look Into The Past
In the famous madeleine scene in the first volume of his Recherche, Marcel Proust posits sensory perception as a trigger of memory. But, when nothing subsists of an old past, more persistent, more faithful, smell and taste still remain for a long time, like souls, remembering, waiting, hoping . This access to the debris of encoded memory content via sensory perception well-known as the “madeleine effect” or “Proust effect” makes the loss of the sense of smell, a typical initial manifestation of Alzheimers disease, appear particularly serious.
The more the individual living with dementia is deprived of core functions of his or her personality beginning with orientation the more painfully he or she is exposed to the danger of a practical loss of dignity. Basic affective-motivational and attentional systems, including positive affect/approach, fear, frustration/anger, and effortful control represent the core of the individuals personality. Especially in the early stages of dementia, the persons concerned become aware of the deterioration of these functions which they might perceive themselves as a loss of dignity.
How Far Have We Come
People have always had dementia over the past hundred years, ever since the time that Alois Alzheimer first described the first case, now 110 years ago. We used to call dementia hardening of the arteries or senile dementia. It was not until the mid 1980s that we were able to make distinctions about defining a diagnosis of Alzheimers. At that point, we were able to make a distinction that abnormal proteins called amyloid and tau were the hallmarks of the changes in the brain in Alzheimers. Since that time, most of the current investigative therapies have been directed at trying to stop the toxic amyloid from building up or dissolving pre-existing plaques. Similarly, new treatments are also directed at stopping tau proteins from forming or dissolving pre-existing proteins. The current medications that are now available, Aricept, Exelon pills and patch, galanthamine and Namenda, are all, unfortunately, symptomatic, short-lived band-aids. You get a little bang for your buck early, and then as time goes on, they are better than nothing, but they become like spitting in the wind. People do get some positive effect for 6 to 12 months, but only in 50% of the people. None of these drugs are designed to disrupt amyloid or tau, which are the primary causes of the disease.
Over the past 15 years, there have been numerous attempts to study and get approval of drugs that will dissolve amyloid, or stop it from forming, or alternatively, stop tau from forming or try to dissolve it.
Also Check: Did Margaret Thatcher Have Alzheimer’s
Oxidative Stress And Damage
Oxidative damage occurs in AD. Studies have demonstrated that an increase in oxidative damage selectively occurs within the brain regions involved in regulating cognitive performance.
Oxidative damage potentially serves as an early event that then initiates the development of cognitive disturbances and pathological features observed in AD. A decline in protein synthesis capabilities occurs in the same brain regions that exhibit increased levels of oxidative damage in patients with mild cognitive impairment and AD. Protein synthesis may be one of the earliest cellular processes disrupted by oxidative damage in AD.
Oxidative stress is believed to be a critical factor in normal aging and in neurodegenerative diseases such as Parkinson disease, amyotrophic lateral sclerosis, and AD. Formation of free carbonyls and thiobarbituric acid-reactive products, an index of oxidative damage, are significantly increased in AD brain tissue compared with age-matched controls. Plaques and tangles display immunoreactivity to antioxidant enzymes.
Multiple mechanisms exist by which cellular alterations may be induced by oxidative stress, including production of reactive oxygen species in the cell membrane . This in turn impairs the various membrane proteins involved in ion homeostasis such as N -methyl-D-aspartate receptor channels or ion-motive adenosine triphosphatases.
Alzheimer’s Disease: The Progress Of Naming
Alzheimer’s Disease is named after the widely known doctor who focused on the study of neurosyphilis and vascular dementia. He reported the first case to the academic world. As Alzheimer’s disease is common in contemporary medicine, the origin and progress of naming, Alzheimer’s Disease, are described in detail.12,13,14,15,16,17,18,19
Don’t Miss: What Alzheimer’s Feels Like From The Inside
Support For Family And Friends
Currently, many people living with Alzheimers disease are cared for at home by family members. Caregiving can have positive aspects for the caregiver as well as the person being cared for. It may bring personal fulfillment to the caregiver, such as satisfaction from helping a family member or friend, and lead to the development of new skills and improved family relationships.
Although most people willingly provide care to their loved ones and friends, caring for a person with Alzheimers disease at home can be a difficult task and may become overwhelming at times. Each day brings new challenges as the caregiver copes with changing levels of ability and new patterns of behavior. As the disease gets worse, people living with Alzheimers disease often need more intensive care.
What Is Alzheimer’s Disease
Alzheimers disease is a brain disorder that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks. In most people with the disease those with the late-onset type symptoms first appear in their mid-60s. Early-onset Alzheimers occurs between a persons 30s and mid-60s and is very rare. Alzheimers disease is the most common cause of dementia among older adults.
The disease is named after Dr. Alois Alzheimer. In 1906, Dr. Alzheimer noticed changes in the brain tissue of a woman who had died of an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps and tangled bundles of fibers .
These plaques and tangles in the brain are still considered some of the main features of Alzheimers disease. Another feature is the loss of connections between nerve cells in the brain. Neurons transmit messages between different parts of the brain, and from the brain to muscles and organs in the body. Many other complex brain changes are thought to play a role in Alzheimers, too.
This damage initially takes place in parts of the brain involved in memory, including the entorhinal cortex and hippocampus. It later affects areas in the cerebral cortex, such as those responsible for language, reasoning, and social behavior. Eventually, many other areas of the brain are damaged.
Also Check: What Do People With Dementia Think
Age Distribution For Alzheimer Disease
The prevalence of AD increases with age. AD is most prevalent in individuals older than 60 years. Some forms of familial early-onset AD can appear as early as the third decade, but familial cases constitute less than 10% of AD overall.
More than 90% of cases of AD are sporadic and occur in individuals older than 60 years. Of interest, however, results of some studies of nonagenarians and centenarians suggest that the risk may decrease in individuals older than 90 years. If so, age is not an unqualified risk factor for the disease, but further study of this matter is needed.
Savva et al found that in the elderly population, the association between dementia and the pathological features of AD is stronger in persons 75 years of age than in persons 95 years of age. These results were achieved by assessing 456 brains donated to the population-based Medical Research Council Cognitive Function and Ageing Study from persons 69-103 years of age at death.
Studies have demonstrated that the relationship between cerebral atrophy and dementia persist into the oldest ages but that the strength of association between pathological features of AD and clinical dementia diminishes. It is important to take age into account when assessing the likely effect of interventions against dementia.
What We Know Today
Through the 1990s, the disease was better understood but, unfortunately, despite exhaustive research over the past 50 years, the cause of Alzheimers disease remains unknown. More importantly, there is no treatment that can reverse or slow down the progression of the disease. The currently available drugs only manage the symptoms, and they do not work for everyone. They can also have unpleasant adverse side effects. It seems we are slowly getting there, however, as more population data now indicate that rather than focusing on drugs, a lifestyle change may help prevent Alzheimers disease in the first place. Large-scale population studies have revealed that individuals who abide by a healthy diet and adopt a positive lifestyle have a much lower risk of Alzheimers disease than populations who smoke, eat an unhealthy diet, and do not exercise. Strategies to alter the progression and prevention of Alzheimers disease via lifestyle changes are already in progress but only time will tell if this is the best approach. With no good treatments available, we have nothing to lose by walking more, controlling high blood pressure, eating a healthy diet, and shedding weight. Not only does this lifestyle reduce the risk of Alzheimers disease, but it also greatly nurtures the brain and body, and improves the quality of life.
Also Check: Can A Person With Dementia Drink Alcohol
The First Use Of Alzheimers Disease
Alzheimer later published his descriptions of several similar patients in 1909 and Kraepelin included Ms. Deters case in the 1910 edition of his widely respected psychiatry textbook. It was Kraepelin who named this dementia after his junior colleague.Auguste Deter was not an elderly woman at the onset of her illness, and Alzheimers disease was therefore regarded as a presenile dementia to distinguish it from the familiar senile dementia thought to result from aging-related vascular disease. Further investigation, however, showed that plaques and tangles were present in the brains of the majority of older adults with symptoms of dementia.
In the late 1960s, the British psychiatrists Tomlinson and Roth described the importance of these plaques in older adults, and in 1970 Dr. Roth questioned the meaningfulness of the age criterion that distinguished AD from senile dementia of the Alzheimers type.
What Is Known About Reducing Your Risk Of Alzheimers Disease
The science on risk reduction is quickly evolving, and major breakthroughs are within reach. For example, there is growing evidence that people who adopt healthy lifestyle habits like regular exercise and blood pressure management can lower their risk of dementia. There is growing scientific evidence that healthy behaviors, which have been shown to prevent cancer, diabetes, and heart disease, may also reduce risk for subjective cognitive decline. To learn more about the current state of evidence on dementia risk factors and the implications for public health, please read the following summaries on Cardiovascular Health, Exercise, Diabetes and Obesity, Traumatic Brain Injury , Tobacco and Alcohol, Diet and Nutrition, Sleep, Sensory Impairment, and Social Engagement or the Compiled Report .
Also Check: How Can A Gp Help Someone With Dementia
Other Important Alzheimers Research And Discoveries
In the years since Dr. Alzheimers initial discovery, the growing realization of how many people are affected by the disease and increased access to improved technology to study it have combined to influence advanced and dedicated research efforts to learn more.
While theres still a lot we havent figured out about Alzheimers disease, there have been a few notable discoveries along the way.
What Is The Burden Of Alzheimers Disease In The United States
- Alzheimers disease is one of the top 10 leading causes of death in the United States.2
- The 6th leading cause of death among US adults.
- The 5th leading cause of death among adults aged 65 years or older.3
In 2020, an estimated 5.8 million Americans aged 65 years or older had Alzheimers disease.1 This number is projected to nearly triple to 14 million people by 2060.1
In 2010, the costs of treating Alzheimers disease were projected to fall between $159 and $215 billion.4 By 2040, these costs are projected to jump to between $379 and more than $500 billion annually.4
Death rates for Alzheimers disease are increasing, unlike heart disease and cancer death rates that are on the decline.5 Dementia, including Alzheimers disease, has been shown to be under-reported in death certificates and therefore the proportion of older people who die from Alzheimers may be considerably higher.6
Recommended Reading: When A Loved One Has Dementia
Neurofibrillary Tangles And Senile Plaques
Plaques are dense, mostly insoluble deposits of protein and cellular material outside and around the neurons. Plaques are made of beta-amyloid , a protein fragment snipped from a larger protein called amyloid precursor protein . These fragments clump together and are mixed with other molecules, neurons, and non-nerve cells .
In AD, plaques develop in the hippocampus, a structure deep in the brain that helps to encode memories, and in other areas of the cerebral cortex that are used in thinking and making decisions. Plaques may begin to develop as early as the fifth decade of life. Whether Ab plaques themselves cause AD or whether they are a by-product of the AD process is still unknown. It is known that changes in APP structure can cause a rare, inherited form of AD.
Tangles are insoluble twisted fibers that build up inside the nerve cell. Although many older people develop some plaques and tangles, the brains of people with AD have them to a greater extent, especially in certain regions of the brain that are important in memory. There are likely to be significant age-related differences in the extent to which the presence of plaques and tangles are indicative of the presence of dementia.
SPs also accumulate primarily in association cortices and in the hippocampus. Plaques and tangles have relatively discrete and stereotypical patterns of laminar distribution in the cerebral cortex, which indicate predominant involvement of corticocortical connections.