Alzheimer's Disease

Alzheimer’s Disease is a cognitive disorder affecting memory, planning, and execution abilities. Learn more about Alzheimer’s stages, early symptoms, and biomarkers here. 

What Is Alzheimer's Disease?

Alzheimer’s is the most common type of neurodegenerative disease. It is a cognitive disease, meaning Alzheimer’s impacts cognitive functions, such as memory, language, planning, and spatial organization.

Alzheimer’s is a prion-related disease, which affects each individual differently. For example, ten people with the same genetics could have ten different outcomes and ten different biomarker profiles.

For some, the disease could progress fast, for others slow. Some could have symptoms show up when they are in the 60’s (or earlier), while others would not show signs of symptoms until in the 90’s.

How Alzheimer’s Affects Us

Regardless of socioeconomic status, ethnicity and gender, Alzheimer’s impacts us all the same. From celebrities to citizens, athletes to leaders, this insidious disease ravages the human brain, giving each person a unique biomarker profile. Remember our beloved ones as they say silently:

I’m still here. I’m still me.

Amprion - public figures affected by Alzheimers - Glen Campbell, Ronald Regan, Rita Hayworth

How Alzheimer’s Affects Us

Regardless of socioeconomic status, ethnicity and gender, Alzheimer’s impacts us all the same. From celebrities to citizens, athletes to leaders, this insidious disease ravages the human brain, giving each person a unique biomarker profile. Remember our beloved ones as they say silently:

I’m still here. I’m still me.

Key Alzheimer’s Statistics

About 6 million people are currently diagnosed with Alzheimer’s in the US alone, with nearly 1 million new Alzheimer’s cases or other dementias per year.

Of the 60 million people aged 65+ in the US (estimated 2020), about 20%, or 12 million, show symptoms consistent with the earliest form of cognitive impairment.

About one-third of these 12 million people will improve over time, while approximately one-third will progress quickly to dementia, and another one-third will remain mildly to moderately impaired.

A 2016 survey of 403 US physicians actively diagnosing or treating Alzheimer’s (published by Medscape) indicated the following:

  • 29% of physicians surveyed believed that the onset of Alzheimer’s could be prevented
  • 77% believed that lifestyle changes could slow progression.
  • 74% of physicians believed that Alzheimer’s is due to “Beta-amyloid and Tau proteins propagating in a prion-like manner.”

(The State of Alzheimer Disease Care: Physicians Weigh In) Bret S. Stetka, MD; Gary W. Small, MD | February 24, 2016)

Four Stages Of Alzheimer's

There are four critical stages of Alzheimer’s disease, representing symptom progression that affect our daily lives.

  1. The Prodromal Stage represents the earliest stage of Alzheimer’s disease before losing memory or executive function (planning and execution). Prodromal disease detection relies on laboratory tests and machine learning algorithms.
  2. Minimal Cognitive Impairment (MCI) – MCI diagnosis reflects the earliest measurable memory loss and mild cognitive decline. There is significant overlap at this stage with normal aging and other non-progressive causes of dementias—approximately one-third of patients with MCI progress to clinical Alzheimer’s within five years.
  3. Clinical Stage – The Alzheimer’s patient shows noticeable memory loss, disorientation, and a decreasing ability to live independently. Drugs such as Namenda may provide short term improvement.
  4. Advanced Stage – In addition to rapidly increasing dementia, patients may show progressive motor dysfunction and loss of autonomic control (including incontinence) resembling Parkinson’s Disease.

Signs of Alzheimer's

What are the major symptoms of Alzheimer’s by stage?

Prodromal Stage

During the earliest Prodromal stage, doctors mainly rely on machine learning algorithms, laboratory biomarkers, and sensors to diagnose speech and movement symptoms.

  • Speech pattern analysis
  • Machine interpretation of MRI and PET scans
  • Retina scanning
  • Position and motion sensors to detect pacing and movements
  • Detection of biomarkers in CSF and blood

Clinical Stage

In the clinical stage, doctors currently employ cognitive tests to diagnose various symptoms.

Soon, Amprion and others will offer biomarker tests to detect misfolded Abeta and Tau, allowing doctors to diagnose Alzheimer’s more accurately.

Alzheimer's Biomarkers

So far, scientists have discovered that most, if not all, neurodegenerative diseases are caused by misfolded forms of normal brain proteins that spread throughout the brain and destroy nerve cells and their connections.

Only a small number of misfolded proteins in the brain can migrate from cell to cell and convert normal proteins to misfolded forms. These self-replicating forms of normal proteins are called prions.

Research and clinical studies on Alzheimer’s patients’ brains show an abundance of the following two misfolded proteins in all Alzheimer’s patients:

  • Abeta
  • Tau

Research also finds two more misfolded protein biomarkers among 20-40% of Alzheimer’s patients:

  • Synuclein
  • TDP43

Consequently, to diagnose Alzheimer’s accurately, doctors will need to order all four biomarker tests:

  • Abeta
  • Tau
  • Synuclein
  • TDP43

Prion Biomarkers: Misfolded Synuclein, Abeta & Tau Proteins

Amprion hero images Misfolded Protein

Prion Biomarker: TDP-43

TDP-43-Protein_TARDBP_PDB_1wf0 - Credits By Emw - Own work, CC BY-SA 3.0, https:::commons.wikimedia.org:w:index.php?curid=8821819

What Are Plaque And Tangles?

Historically, plaque and tangles are the biomarkers for Alzheimer’s diagnosis. Plaque and tangles are large insoluble aggregates of misfolded proteins detectable under the microscope.

  • Plaque results from the clumping of Abeta prion-proteins.
  • Tangles result from the clumping of Tau prion-proteins.

The plaque represents large insoluble clumps of misfolded Abeta between brain cells.

Tangles represent insoluble clumps of misfolded tau within brain cells.

Plaque Caused By Abeta

Plaque Caused By Abeta

Tangles Caused By Tau

tau misfolded protein

When Are Plaque and Tangles Formed?

When misfolded Abeta or Tau first appear in the cerebral spinal fluid (CSF), one can expect plaque/tangles to form several years later. The first symptoms may not be present for several decades. This long incubation/ development period is a hallmark characteristic of prion-proteins, making them a potent neuron-destroying force.

In Alzheimer’s patients, the protein misfolding may begin as early as youth or early adulthood between 30 and 40.

Once the prion-proteins form, the misfolding process replicates and spreads over a long development cycle, damaging the brain for decades without symptoms. During this asymptomatic stage, the destruction of brain cells occurs silently. Clinical signs appear decades later.

What Causes Alzheimer's?

Many different life-events may trigger the appearance of misfolded abeta and tau and set the conditions for Alzheimer’s in motion. Some of these events are unavoidable, while others may require careful planning and lifestyle adjustments. The following factors are known to increase the risk of Alzheimer’s:

Genetics

  • Individuals with Dominant Inherited Alzheimer’s (DIA) carry a single gene that encodes a mutated Abeta protein with an increased ability to misfold spontaneously. These patients have misfolded Abeta from birth and onward but do not exhibit clinical symptoms until approximately 35. DIA is relatively rare in the population.
  • Individuals carrying the ApoE4 gene variant have a significantly increased risk of Alzheimer’s in their lifetime, and they tend to get the disease earlier compared with non-carriers. The ApoE4 gene is relatively common and appears in approximately 14% of people.

Past infection history with certain viruses and bacteria 

  • Previous infection with Herpesviruses may drive Alzheimer’s later in life. The viral effects may be due to chronic inflammation in the brain.
  • Previous infection with certain bacteria, most notably cyanobacteria, has also been proposed as a predisposing factor for Alzheimer’s. Cyanobacteria infection in both the brain and the gut may play a role.
  • The link between gut bacteria and neurodegenerative disease drives new therapeutics directed against toxic gut bacteria.

Repeat traumatic head injury

Alzheimer’s appears more frequently in individuals with histories of repeated head trauma. These include athletes in contact sports, soldiers, and people whose jobs predispose them to repeated head trauma and concussions.

Unhealthy lifestyles/habits

  • Smoking, unhealthy diets, and lack of exercise may predispose individuals to Alzheimer’s plus cardiovascular, kidney, and lung disease.
  • Chronic inflammation may link unhealthy lifestyles to Alzheimer’s.

What Causes Dementia In Alzheimer's?

Research & clinical studies indicate that the following misfolded proteins  may promote loss of brain cells, leading to cognitive decline in Alzheimer’s:

  • Misfolded beta-amyloid (abeta) in the form of amyloid plaque (plaque),
  • Misfolded tau in the form of neurofibrillary tangles (tangles)

Alzheimer’s patients show the presence of both plaque and tangles in the brain. However, the presence of either tangles or plaque alone does not warrant a diagnosis of Alzheimer’s.

Therefore, contrary to conventional belief, the mere presence of Amyloid plaque (misfolded Abeta) in the brain, by itself, is not a definitive sign of Alzheimer’s disease.

Other misfolded proteins, including Synuclein and TDP-43, may also play a role in driving the progression of Alzheimer’s and different types of dementia. To develop personalized drugs and treatments to slow or stop the decline of Alzheimer’s, doctors will need a complete biomarker profile for each person.

Alzheimer's Brain Damage On A Molecular Level

Alzheimer’s tends to cause widespread damage in the brain, affecting many different regions, mainly in the cerebral cortex. Other neurodegenerative diseases tend to cause localized damages in the brain.

Why does Alzheimer’s tend to be more widespread in the brain?  One possibility is that high levels of abeta-type prions in the spinal fluid (CSF) distribute Alzheimer’s damage widely throughout the brain extracellularly (rather than spreading locally from cell to cell).

In Alzheimer’s disease, misfolded tau seems to be the bad actor that causes direct brain damage leading to cognitive and motor decline.

  • Tau appears prominently in the brain regions where maximum cell loss occurs. The resulting damage and cell loss cause the brain to shrink in severe Alzheimer’s cases.
  • In the absence of plaque, Tau tangles cause progressive cognitive and motor damage to the brain in other forms of non-Alzheimer’s dementia.
  • In the absence of tangles, Plaque frequently appears in elderly individuals without signs of dementia or cognitive decline.

Other Type of Dementias

Tau tangles alone appear sufficient to induce progressive neurodegenerative disease, called Tauopathy, which is different from Alzheimer’s. Tauopathy brain damage generally localizes to one or two regions in the brain.

Research estimates that misdiagnosis of Alzheimer’s is between 20 to 50%! Why is Alzheimer’s diagnosis so challenging?
Because in prion-related diseases, the bad actors or misfolded proteins are impossible to detect using conventional methods. Thanks to the advancement in molecular science, we can now detect the misfolded proteins early and accurately. 

Discover our breakthrough biomarker testing here.

lewy body dementia

Research estimates that misdiagnosis of Alzheimer’s is between 20 to 50%! Why is an accurate diagnosis of Alzheimer’s so challenging?
Because in prion-related diseases, the bad actors or misfolded proteins are impossible to detect using conventional methods. Thanks to the advancement in molecular science, we can now detect the misfolded proteins early and accurately. 

Discover our breakthrough biomarker testing here.

How Is Alzheimer's Diagnosed?

Historically, Alzheimer’s disease is diagnosed based on symptoms. When patients suspect some level of loss of cognitive functions, such as memory loss, they visit the doctor’s office for tests, including the following:

Clinical Observations Based On Cognitive Tests

Currently, Alzheimer’s diagnoses rely primarily on cognitive symptoms.

PET- / MRI Scans

Doctors employ PET Scanning to detect plaque and tangles. First, radioactive tracers specific for misfolded abeta or misfolded tau are injected into the patient’s body, immediately followed by brain imaging. MRI scans reveal early structural damage to the brain. In some cases, MRI may also show early damage to blood vessels and the blood-brain-barrier.

Biomarker Test

Amprion anticipates the launch of various biomarker tests to diagnose Alzheimer’s within the next 12 months. These biomarker tests will provide the most accurate and early-stage Alzheimer’s diagnosis on the molecular level.  Learn more about our Alzheimer’s test here.

Alzheimer's Misdiagnosis

Every Alzheimer’s patient has a unique biomarker profile, making Alzheimer’s disease extremely challenging to detect in the early stages. The presence or absence of plaque alone is inconclusive for an Alzheimer’s diagnosis. 

Consider these statistics:

  • About 20% of healthy people aged 80+ have plaque but no dementia.
  • Nearly 20% of patients have dementia but no plaque.

Rampant misdiagnosis of Alzheimer’s is the problem we are solving through biomarker testing.

Did you know that one-third of the people with Minimal Cognitive Impairment (MCI), the earliest symptomatic stage for Alzheimer's and other dementias, go on to live healthy lives free from Alzheimer's! Isn't that wonderful news?

Treatment For Alzheimer's

There are currently no treatments that slow or stop the progression of Alzheimer’s, despite decades and billions spent in drug development and clinical trials. We are working hard to change that.

There are currently drugs that aim to remove plaque; however, these drugs have been ineffective in stopping or delaying Alzheimer’s at late stages.

The ability to diagnose Alzheimer’s in the early stages empowers molecular science to accelerate drug and treatment developments for Alzheimer’s.

For those looking for help and support, check out our Alzheimer’s Research & Treatment Center Directory and other community resources for Brain Health.

To develop treatments for Alzheimer’s, we need on-going diagnostic data to monitor patients’ prion formation levels and how aging affects the disease’s progression. 

We empower drug companies to expedite successful drug development by selecting targeted patient samples for clinical trials through our biomarker detection.

alzheimer's biomarker profile

To develop treatments for Alzheimer’s, we need on-going diagnostic data to monitor patients’ prion formation levels and how aging affects the disease’s progression. 

We empower drug companies to expedite successful drug development by selecting targeted patient samples for clinical trials through our biomarker detection.

Early Onset of Alzheimer's

Early-onset Alzheimer’s is relatively rare, about 5% of all Alzheimer’s patients.

Most patients with early-onset Alzheimer’s disease have a genetic predisposition to the disease. Mutations or extra copies of the gene encoding abeta are a significant cause. These include patients with Dominantly Inherited Alzheimer’s and Down’s Syndrome.

Also, people carrying the ApoE4 gene tend to have an earlier onset of Alzheimer’s symptoms.

Dementias of the non-Alzheimer type, including Frontotemporal dementia and Lewy Body dementia, tend to show symptoms at earlier ages than Alzheimer’s.

Delay Onset of Alzheimer's Symptoms

According to the Alzheimer’s Association, delaying the onset of Alzheimer’s by just five years could decrease the number of people with an active disease by as much as 42%

delay onset of alzheimer's

Delay Onset of Alzheimer's Symptoms

According to the Alzheimer’s Association, delaying the onset of Alzheimer’s by just five years could decrease the number of people with an active disease by as much as 42%

With the help of early detection biomarker tests, we aim to delay the onset of clinical symptoms by years or even decades.

Are you interested in taking your knowledge of Alzheimer’s for a test drive?  Take Alzheimer’s Quiz here.

6 Lifestyle Changes to Delay the Onset of Alzheimer's

  1. Exercise regularly
  2. Healthy diet
  3. Stop smoking
  4. Maintain social activities
  5. Keep intellectually engaged through reading and hobbies, and
  6. Maintain emotional and mental health.

Is Alzheimer's Hereditary?

Alzheimer’s is mainly a sporadic disease, meaning that genetics may increase the risk of Alzheimer’s, but is not the primary determinant.

Scientists have discovered a gene called ApoE4, which increases the risk of Alzheimer’s. However, most people carrying one copy of the ApoE4 gene will not exhibit the disease in their lifetime.

Alzheimer's Frequently Asked Questions

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.

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 of 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-iike 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.

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 as well as 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 to10-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 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 radioactivestudies 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 brainparticularly 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.

Did you know that the gene ApoE4 affects women more severely than men? Scientists are trying to understand why.