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 (this may be a new term for you, learn more about prion-proteins here), 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 may show symptoms in their 60’s (or earlier), while others may not manifest signs until they are much older.

Key Alzheimer’s Statistics

For those drawn to numbers, you’ll love this section. For those who get dizzy seeing stats, prepare yourself!  (Pocket calculator recommended!) Here we go.

Currently, there are about 6 million people diagnosed with Alzheimer’s in the US alone. Every year, this existing patient pool increases by nearly 1 million.

Of the 60 million people aged 65+ in the US, about 12 million show early cognitive impairment symptoms. (Hello, are you still with me?) 😉

About 1/3 of these 12 million people will improve over time, while about 1/3 will progress quickly to dementia, and the rest will remain mildly to moderately impaired.

Can you imagine the peace of mind early detection would bring? It’s far better to know than to wonder. 

A 2016 Medscape survey of hundreds of U.S. physicians who actively diagnose/treat Alzheimer’s found the following:

  • 29% believed the onset of Alzheimer’s could be prevented
  • 77% believed lifestyle changes could slow the progression
  • 74% believed Alzheimer’s is due to misfolded Abeta and Tau proteins

See, that was a lot of numbers, right? Kudos for hanging in there. Optional pop quiz if you’re into that kinda thing. 😜

Here are the chapter summaries of the serious story behind these stats:

  1. Alzheimer’s is a growing health crisis that affects all of us as we age.
  2. If we identify Alzheimer’s early in life, we’re in a position to do something about it – Course-correct the disease.
  3. And yes, we are empowering people to do exactly that!

How Alzheimer’s Affects Us

Regardless of socioeconomic status, ethnicity, and gender, Alzheimer’s impacts us all the same.

From celebrities to citizens, leaders to line-dancers, this insidious disease ravages the human brain, giving each person a unique biomarker profile.

Can you hear our loved ones silently calling out to us:

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, leaders to line-dancers, this insidious disease ravages the human brain, giving each person a unique biomarker profile.

Can you hear our loved ones silently calling out to us:

I’m still here. I’m still me.

Stages of Alzheimer's

You may read there are anywhere from 3 to 7 stages of Alzheimer’s. To keep things simple, here are the 4 critical stages, each representing symptom progression.

The Prodromal Stage

(Try casually slipping this nerdy word in during your next Zoom meeting to impress your friends) 😄

This is the earliest stage of Alzheimer’s before losing memory or executive functions such as planning. Prodromal disease detection relies on laboratory tests and machine learning algorithms.

Minimal Cognitive Impairment (MCI)

MCI diagnosis reflects the earliest measurable memory loss and mild cognitive decline. This stage has significant overlap with normal aging and other non-progressive dementias—approximately one-third of patients with MCI progress to clinical Alzheimer’s within five years.

Alzheimer’s patients are often misdiagnosed using conventional testing at this stage.

Clinical Stage

The Alzheimer’s patient shows noticeable loss of memory, orientation, and the ability to live independently. Several widely available drugs may provide short-term improvement at this stage. Imaging studies show substantial formations of both plaque (produced by Abeta) and tangles (formed by Tau).

Advanced Stage

In addition to rapidly increasing dementia, patients may show progressive motor dysfunction (Parkinson’s-like) and diminished autonomic controls, such as bowel/bladder.

Signs of Alzheimer's

Alzheimer’s disease causes your brain to shrink and its cells to die. It affects all factors of your life, including the most basic ones.

What’s the First Sign of Alzheimer’s Disease?

The first and most noticeable sign of Alzheimer’s disease is basic forgetfulness. What may look like normal memory lapses become more frequent, such as forgetting names or recent events. The person might become aware of his/her memory issues, but loved ones notice it sooner.
Top 10 Warning Signs of Alzheimer's Disease
Top 10 Warning Signs of Alzheimer's Disease

Alzheimer's Biomarkers

Before we dive into biomarkers, let’s paint a picture of how Alzheimer’s damages brain cells.  

So far, scientists have discovered that Alzheimer’s is caused by misfolded proteins, which spread throughout the brain, destroying nerve cells and their connections.

Misfolded proteins can convert and corrupt normal proteins to misfold and self-replicate. These are also called prion-proteins.

Research on Alzheimer’s patients’ brains show an abundance of the following two misfolded protein biomarkers:

  • Abeta
  • Tau

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

  • Synuclein
  • TDP43

To diagnose Alzheimer’s accurately, doctors will need to order all four Alzheimer’s biomarker tests.

Alzheimer's Biomarkers: Misfolded Synuclein, Abeta & Tau

Amprion hero images Misfolded Protein

Alzheimer's 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?

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

  • Abeta prion-proteins cause plaque.
  • Tau prion-proteins form tangles.

Plaque represents large insoluble clumps of misfolded Abeta between brain cells.

Tangles are insoluble clumps of misfolded Tau within brain cells.

Abeta Causes Plaque

Plaque Caused By Abeta

Tau Forms Tangles

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 during young adulthood between 30’s and 40’s.

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 many years later.

What Causes Alzheimer's?

The short answer is–we are not entirely sure what causes Alzheimer’s….yet. However, research shows many different life-events may trigger the start of Abeta and Tau misfolding and set the conditions for Alzheimer’s in motion. Some of these events are unavoidable.

Alzheimer’s Risk Factors

Several risk factors contribute to the probability of developing Alzheimer’s disease. Aside from aging and family history (especially if a first-degree family member has been affected, such as a sibling or a parent) being the key risk factors, other major Alzheimer’s risks include the following: 

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 aged 35. Thankfully, DIA is relatively rare, about .01 percent of the population.
  • Individuals carrying the ApoE4 gene variant have a significantly increased risk of Alzheimer’s in their lifetime. They tend to get the disease earlier compared with non-carriers. The ApoE4 gene is relatively common and appears in approximately 14% of the population.
  • People with down syndrome also have high risks of developing Alzheimer’s disease. In fact, they can begin to show signs 10 or 20 years earlier than normal. 

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 for individuals with histories of repeated head trauma. These include athletes playing contact sports, soldiers, and people working in jobs with high-risk of repeated concussions.

Rugby Players

Unhealthy lifestyles including:

  • Smoking (2x the risk!)
  • Unhealthy diets (bacon/fried twinkies at every meal?) 🥓
  • Lack of exercise (Don’t just watch sports, get out there!) 🤽🏽‍♀️🤾🏻‍♂️🚴‍♂️
  • Bad sleeping habits (Seriously, 2 episodes max per night. You know who you are.)
  • Excessive alcohol consumption (Your personality is dynamite without overdoing the alcohol.)

Anxiety and stress

Anxiety makes your brain live in a constant state of stress and panic, causing your brain to age faster. Anxiety also reduces cognitive function and harms your memory.

So a friendly reminder for you: Take it easy every day. Work-out (physical and mental), laugh and eat healthily. Remember the song “Be Happy?”  🤣 🥦 🤺

What Drives Alzheimer's Progression?

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

  • Misfolded Abeta in the form of amyloid Plaque 
  • Misfolded Tau in the form of neurofibrillary Tangles

Although Alzheimer’s patients show the presence of both Plaque and Tangles in the brain, the presence of either one does not warrant a diagnosis of Alzheimer’s.

Therefore, contrary to conventional belief, the mere presence of Plaque in the brain, by itself, is not a definitive diagnosis of Alzheimer’s.

Other misfolded proteins, including Synuclein and TDP-43, may also play a role in driving the progression of Alzheimer’s and other dementias.

Alzheimer's Brain Damage on a Molecular Level

Hey, great to see you made it this far. Pat yourself on the back. 😄 Grab a refreshment drink and carry on. Deep stuff ahead. ⬇️

Alzheimer’s tends to cause widespread damage in the brain, affecting many regions in the cerebral cortex compared to other brain diseases. 

Why does Alzheimer’s tend to cause more widespread havoc in the brain? One possibility is that high levels of Abeta-type prions in the spinal fluid distribute the disease extracellularly instead of spreading it locally from cell to cell. (Think of it as a tiny biological Jumping Jack leaping around the brain, spreading misery as it goes.) 🤸🏿‍♀️🤸🏼‍♂️

In Alzheimer’s disease, misfolded Tau seems to cause direct brain damage leading to cognitive and motor decline.

  • Tau prion-proteins appear prominently in the brain regions where maximum cell loss occurs, causing 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 non-Alzheimer’s dementia.
  • In the absence of Tangles, Plaque frequently appears in elderly individuals without signs of dementia or cognitive decline.

Tauopathy

Tau tangles alone appear sufficient to cause progressive neurodegenerative disease, known as Tauopathy. A different form of dementia, Tauopathy, causes localized damage in one or two regions in the brain.

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.

During the early stages, doctors mainly rely on machine learning algorithms, speech pattern analysis, and sensors to diagnose speech and movement symptoms. These methods include machine interpretation of MRI and PET scans, retina scanning, position and motion sensors to detect pacing and movements. In later stages, doctors employ cognitive tests to diagnose various symptoms. 

Clinical Observations Based On Cognitive Tests

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

PET/MRI Scans

Doctors employ PET/MRI 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. 

PET/MRI Scans run about $5,000 and $2,500, respectively. If the results reveal Plaque and Tangles, it’s costly confirmation that irreversible brain destruction has already occured.

This is too late!

Biomarker Test

That was all in the past! Ready for the new frontier? 😄 Let’s start with a story.

Normandy – where the Allies first secured a beachhead, allowing them to push towards Germany and ultimately win World War II.

The war against Alzheimer’s has been raging for over 120 years! Finally, we have landed our equivalent of a Normandy beachhead – Biomarker Testing!

Four (4) misfolded proteins are making up the enemy force. Until now, science has only been able to identify these bad guys in deceased victims’ brains. 😢

Our breakthrough biomarker testing traces misfolded Synuclein, 1 of the 4 biomarkers in its early stages.

This pivotal achievement sets up a final mission –
Detect the remaining rogue agents, and push onwards to victory: A CURE.

Amprion expects to roll out commercially all 3 remaining biomarker tests soon. 

Research estimates that misdiagnosis of Alzheimer’s is between 20 to 50%!

Why is Alzheimer’s diagnosis so challenging?

Because the 4 misfolded proteins are impossible to track using conventional tests.

Thanks to a new breakthrough, we can now accurately detect 1 of the 4 misfolded proteins early!

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.

Misdiagnosis

Every Alzheimer’s patient has a unique biomarker profile. This makes the disease extremely challenging to detect, especially at the early stages.

Did you know that 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.

Biomarker testing aims squarely to STOP the rampant Alzheimer’s misdiagnosis. 🛑 ✋🏾🔚

Treatment for Alzheimer's

Sorry to be the bearer of sad news. Despite decades and billions spent in drug development and clinical trials, there is no cure – yet.

The culprit? Alzheimer’s has been challenging to accurately diagnose in the past 120 years. Let alone to detect early. UNTIL NOW! 

What is the impact of early detection? Let’s take a look at the shining success of cancer treatments.

Many years ago, when someone found out they had cancer, there was no hope of recovery. Now, most of us know at least one cancer survivor. Isn’t that marvelous?!?

So what changed?

Because in recent years, doctors and scientists have finally been able to detect and analyze cancer in the early stages. Early detection is key. Researchers and scientists get a head-start on drug innovation and find cures. Cancer patients survive and thrive to tell their stories. 

For Alzheimer’s, this is the next frontier!  Early detection empowers us to track down a cure!

Our Ultimate Pursuit > FREE the World of Alzheimer’s!

Personalized medicine requires early detection of your biomarker profile.

This is the nexus to the cure!

We aim to innovate biomarker-targeted drugs, matching the right patients to the right clinical trial.

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

Alzheimer’s early-onset is relatively rare, experienced by about 5% of Alzheimer’s patients.

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

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

For those into Easter egg-hunt, keep going! There are treats ahead. 🌮🍒 🥨 🥐 🍜 🍧

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%

Lifestyle Changes to Delay Alzheimer's Onset

  1. Exercise regularly ⛷🏃🏻‍♂️🏃‍♀️🤺🏄🏻‍♀️🚴‍♀️🏋🏽‍♂️
  2. A healthy diet (eat those broccoli florets!)
  3. Stop smoking (C’mon, you can do it, Ed!)
  4. Maintain social activities (even during Covid, use Zoom if you have to.)
  5. Keep intellectually engaged through reading (like this fantastic page!) 😜
  6. Develop a fun new hobby (camel-racing, anybody?) 🐫 🎤 💃 🐕  🎥  🚴‍♂️  
  7. Maintain emotional and mental health. 😇

See told ya! Treats galore. 🐶

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.

Congrats on making it through all the marvelous material. We hope you enjoyed the read (and the emojis). Grab a cookie and a cuppa! You deserve it. 🍪 🍵 😜

Then come back and go the extra mile for bonus points by perusing the FAQs. 🏃🏻‍♂️🏃‍♀️

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.

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