Alzheimer's FAQ’s

The majority of Alzheimer's cases are sporadic, meaning that there is no known familial or hereditary cause. Hereditary cases of Alzheimer's are relatively rare. The best characterized hereditary cases involve mutations in the Abeta gene that lead to increased misfolding of Abeta and formation of Prion-like particles. However, certain normal gene variants may be inherited that increase the probability that a carrier will have Alzheimer's during their lifetime. People who inherit either one or two copies of the ApoE gene variant ApoE4 have a 3 to 10-fold increased risk of Alzheimer's. Nevertheless, not all patients with ApoE4 develop Alzheimer's, and many Alzheimer's patients do not carry ApoE4.
At present, there is no single test that is sufficient to give a diagnosis of Alzheimer's versus other forms of neurodegenerative disease or dementia. Patients with Alzheimer's show notable differences in several biomarkers, but none of these is sufficient by itself to make a diagnosis. ABETA BIOMARKERS. Normal individuals produce two different sizes of Abeta amyloid (Abeta) in their brains: Abeta 42 and Abeta 40. Some Alzheimer's patients produce large clusters of Abeta 42 in the brains. These clusters are referred to as plaque. Alzheimer's patients with large amounts of plaque show a decreased amount of Abeta 42 in their spinal fluid and blood compared with Abeta 40. The ratio of Abeta 40 to Abeta 42 in blood and spinal fluid can help to diagnose Alzheimer's. However, some older patients without Alzheimer's have both plaque as well as reduced Abeta 42 to 40 ratios. Some Alzheimer's patients without plaque show normal Abeta 42 to 40 ratios. TAU BIOMARKERS. Most patients with Alzheimer's show consistent changes in the structure and location of Tau protein within the brain. Tau in Alzheimer's patients tends to form large clusters referred to as tangles which are distinct from Abeta clusters in plaque. The presence of tangles may lead to reduced levels of Tau in spinal fluid or blood. Tau in tangles also tends to contain certain modifications called phosphorylation. The presence of high levels of phosphorylated Tau in blood or spinal fluid has also been associated with a diagnosis of Alzheimer's. Since no single test appears sufficient for diagnosis, many physicians require a panel of both Abeta and Tau biomarkers, plus clinical and imaging data, to make a definitive diagnosis of Alzheimer's.
At present, there is no reliable and approved method for early detection of Alzheimer's. The early promise of radioactive PET imaging for Abeta has not lived up to expectations. New radioactive tracers targeting misfolded Tau may show more promise, but are unlikely to track the earliest stages of disease in the first few years. Measuring relative amounts of different Abeta fragments and Tau fragments in blood and spinal fluid show some correlation but are insufficient for definitive early diagnosis.
Since many of the symptoms of Alzheimer's appear only after irreversible damage to the brain has occurred, early testing and diagnosis hold the key to both prevention and cure. The earliest known event in the progression of Alzheimer's is the misfolding of Abeta and Tau proteins into Prion-like particles. As a result, the earliest reliable diagnostic methods focus on detection of very small numbers of Prions in the brain and spinal fluid. At intermediate times, the Abeta and Tau Prions will also be detectable in the blood. Both of these tests may lead to early intervention or prevention of clinical disease in the future. Other early changes, such as phosphorylation of Tau, are downstairs from Prion formation but may also be useful for early detection.
There appear to be many different causes of Alzheimer's in different patients. Alzheimer's has been linked to one or more traumatic head injuries, viruses, eating certain plant toxins, genetics, and chronic inflammation. All of these may contribute to triggering the disease. However, in almost all cases, the triggering appears to result in misfolding and aggregation of two different brain proteins, abeta amyloid (Abeta) and tau (Tau). The initial misfolding and aggregation of Abeta and Tau leads to the formation of prion-like particles composed of these proteins which can proliferate and spread between connected nerve cells. The period between the initial misfolding and aggregations of Abeta and Tau and the first appearance of disease is often between 20 and 40 years. The presence of misfolded Abeta and Tau aggregates leads to irreversible damage and death to large numbers of connected brain cells. When the total number of cells destroyed becomes very large, we lose our memories, our ability to navigate, speak, and perform normal activities such as grooming and eating.
Alzheimer's is transmitted like a virus between adjacent, connected nerve cells. As each new cell is affected, it is irreversibly damaged and dies. Over time, the progressive loss of large numbers of nerve cells affects memory and executive function. At late stages of disease, our brains accumulate both large clusters of misfolded Abeta protein in structures called plaque and large clusters of misfolded Tau protein in structures called tangles. At very late stages of the disease, the size of the brain is greatly reduced.
At present, Alzheimer's Disease is not curable. Certain medications are available that help the remaining brain cells to increase their activities, but as more and more cells are lost, these medications lose effectiveness. Drugs targeting misfolded Abeta and Tau are in development, as are drugs targeting inflammation and cell death. Unfortunately, none of these drugs has yet succeeded in clinical trials, but there is hope and expectation for future cures.
Alzheimer's is currently the sixty (6th) leading cause of death in the US, associated with an estimated 100,000 deaths annually. Alzheimer's decreases normal lifespan both directly, through damage to critical pathways in the brain, and indirectly, by reducing our ability to care for ourselves and maintain healthy activity and behaviors.
The majority of Alzheimer's cases are sporadic, meaning that there is no known familiar or hereditary cause. Hereditary cases of Alzheimer's are relatively rare. The best characterized hereditary cases involve mutations in the Abeta gene that lead to increased misfolding of Abeta and formation of Prion-like particles. However, certain normal gene variants may be inherited that increase the probability that a carrier will have Alzheimer's during their lifetime. People who inherit either one or two copies of the ApoE gene variant ApoE4 have a 3 to 10-fold increased risk of Alzheimer's. Nevertheless, not all patients with ApoE4 develop Alzheimer's, and many Alzheimer's patients do not carry ApoE4.
Alzheimer's most likely begins in middle age, but symptoms do not appear until decades later. As a result, most people will notice symptoms only after much of the brain has already been irreversible destroyed. The extensive damage leads to a very general deterioration in high-level thinking and executive function, which we refer to as dementia. Dementia can also result from a number of other injuries and diseases that damage key areas of the brain. These include stroke and vascular disease, as well as infection and chronic inflammation. Other neurodegenerative diseases related to Parkinson's also can result in dementia similar if not identical to Alzheimer's.
Alzheimer's in the brain is associated with three characteristic changes seen by imaging as well as under the microscope. The first characteristic change involves the progressive misfolding and aggregation of the protein Abeta Amyloid ("Abeta"), which occurs primarily in the extracellular space surrounding brain neurons. Large aggregates of misfolded Abeta form within the brain that are recognized as "plaque" both by radioactive studies PET imaging and under the microscope. The second characteristic change is the progressive misfolding and aggregation of the protein Tau, which occurs primarily within neurons. These large Tau aggregates are recognized as "tangles" both by radioactive PET imaging and under the microscope. The third characteristic change is massive loss of neurons in the brain, particularly in regions of tangles. This leads to actual shrinkage of the brain that is detectable by MRI imaging, by visual analysis of and weight of the brain post-mortem, and by microscopic inspection.
Alzheimer's begins with misfolding and aggregation of Abeta and Tau. This process spreads from cell to cell within the brain and results in the death of affected neurons. Late in the process, large aggregates of Abeta and Tau appear within the brain as plaque and tangles, respectively. Once misfolding of Abeta and Tau has begun, the spread and massive neuronal death is a very slow process and takes place over decades. As a result, although Alzheimer's symptoms appear later in life, the disease actually begins for most people in middle age.
Maintaining optimal brain health is critical as a person ages. As you read the article below, you will find that good brain health is possible at 90! Amprion champions early diagnosis for Parkinson's and Alzheimer's, and this important article suggests that the detection of plaque by PET imaging is not sufficient for a diagnosis of Alzheimer's Disease. The data indicate that there is little or no progression of disease in patients >75 years of age with plaque, but no cognitive symptoms. Our research findings conclude that plaque is best viewed as a biomarker linked to Alzheimer's, but insufficient for diagnosis. Our studies also demonstrate that Tau and Synuclein are also key biomarkers for Alzheimer’s and Parkinson’s. Hence, early tests based on these biomarkers are the most accurate diagnosis. Amprion will offer these biomarker testing in early 2021.
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