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Alzheimer's Disease

Alzheimer’s Disease is a cognitive disorder affecting memory, planning, and execution abilities. Discover the 4 stages, 10 symptoms, and key biomarkers. 

Table of Contents

What is Alzheimer's Disease?

It’s the most common type of neurodegenerative disease, affecting cognitive abilities.

Alzheimer’s is a prion disease. There is a lot to learn about prions, aka misfolded proteins, and the role they play in brain diseases.

One of the key characteristics is that it impacts everyone differently. For instance:

Ten people with the same genetic makeup could have ten different outcomes and ten different biomarker profiles.

2-minute Brain Talk Watch and learn how Alzheimer’s affects the brain.

Alzheimer’s Statistics

Currently, in the US alone, there are about 6 million people diagnosed with Alzheimer’s. Every year, nearly 1 million new cases are added to this patient pool.

Of the 60 million people aged 65+ in the US, about 12 million show early cognitive impairment symptoms. Interestingly:

  • 1/3 of these 12 million people will improve over time. 
  • 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 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 could be prevented
  • 77% believed lifestyle changes could slow the progression
  • 74% believed Alzheimer’s is due to misfolded Abeta and Tau proteins

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 the disease early, we’re in a position to do something about it. 
  3. The goal is to delay or stop the onset of symptoms.

Early detection empowers early prevention! 

Alzheimer’s Affects Us All

From celebrities to citizens, leaders to line-dancers, this insidious disease ravages the human brain.

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

Alzheimer’s Affects Us All

From celebrities to citizens, leaders to line-dancers, this insidious disease ravages the human brain.

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

I’m still here. I’m still me.

7 Early signs of Alzheimer's

People in the beginning stage of Alzheimer’s experience a multitude of issues relating to memory and executive function.

Inability to plan

This is most applicable for someone who is usually the planner in the family. If they become reticent or unable to plan, this could be an early sign.

Forgetting recent key events

This is forgetting truly noteworthy, recent events such as a natural disaster like an earthquake.

Trouble managing finances

Having difficulties paying bills and managing accounting matters can be red flags.

Getting lost in the neighborhood

Being confused in previously familiar places. For instance, having trouble finding a way home from weekly tennis playing. 

Skipping social events

Trouble keeping up with conversations is a tell-tale sign. It results from a normally out-going person staying away from regular gatherings.

Losing interest in favorite hobbies

For example, an avid poker player starts missing the weekly game.

Trouble with speaking and writing words

Struggling to remember the right words to communicate, both verbal and written.

Four Stages of Alzheimer's

Here are the 4 critical stages of the disease, each representing symptom progression.

The Prodromal Stage

This is the earliest stage before memory or executive function loss. 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 a significant overlap with normal aging and other non-progressive dementias.

About 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 patient shows a noticeable loss of memory, orientation, and the ability to live independently. Several widely available drugs may provide short-term improvement at this stage. There are likely side effects so please consult your physician.

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.

Ten Symptoms of Alzheimer's

Alzheimer’s affects all factors of your life, including the basics like paying bills. 

The first and most noticeable sign is forgetfulness. What may look like normal memory lapses become more frequent, such as forgetting names or recent events. People living with Alzheimer’s might become aware of their memory issues, but loved ones notice it earlier.

Here are the top ten warning signs:

Top 10 Warning Signs of Alzheimer's Disease
Top 10 Warning Signs of Alzheimer's Disease

Alzheimer's Biomarkers

Let’s first paint a picture of how the disease damages brain cells.  

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 shows there is an abundance of two types of prions in the brains of Alzheimer’s patients:

  • Abeta
  • Tau

In addition, two more prions are found among 20-40% of individuals living with Alzheimer’s:

  • Synuclein
  • TDP43

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

Misfolded Synuclein, Abeta & Tau Proteins

Amprion hero images Misfolded Protein

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 Plaques and Tangles?

Plaques and tangles are currently used as biomarkers for Alzheimer’s diagnosis. They are large insoluble aggregates detectable under the microscope.

  • Misfolded Abeta causes plaques.
  • Misfolded Tau forms tangles.

Plaques develop between brain cells.

Tangles develop within brain cells.

Misfolded Abeta Causes Plaques

Plaque Caused By Abeta

Misfolded Tau Forms Tangles

tau misfolded protein

When Are Plaques and Tangles Formed?

As soon as misfolded proteins appear in the cerebral spinal fluid (CSF), plaques/tangles form several years later. However, symptoms may not appear until decades later.

This long asymptomatic stage is a key characteristic of prions, making them potent neuron-destroyers.

In Alzheimer’s, the initial misfolding of proteins may begin in early adulthood.

Once the misfolded proteins are formed, the process replicates and spreads. During this asymptomatic stage, neuronal destruction occurs silently. Clinical signs appear many years later.

What Causes Alzheimer's?

Science hasn’t figured out the exact cause. However, there appear to be various triggers for different patients including:

  • Traumatic head injuries
  • Viruses
  • Eating certain plant toxins
  • Genetics
  • Chronic inflammation

In almost all cases, these triggers result in the misfolding of Abeta and Tau proteins, forming plaques and tangles, respectively.

How Does Alzheimer's Affect People

The misfolded Abeta and Tau aggregates lead to the death of connected brain cells. When cell death is widespread, we lose our:

  • Memories
  • Ability to navigate
  • Ability to speak
  • Ability to perform normal activities such as grooming and eating

Alzheimer’s affects women more frequently and severely than men.

Alzheimer's Risk Factors

The following are key factors that contribute to an increased 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. They do not exhibit clinical symptoms until about age 35. Thankfully, DIA is relatively rare, about .01 percent of the population.
  • Individuals carrying the ApoE4 gene variant have a significant risk. 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 a high risk. In fact, they may begin to show signs 10 to 20 years earlier than normal.

Past infection history 

  • 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, may also be a factor. 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 a high risk of repeated concussions.

Rugby Players

Unhealthy lifestyles including:

  • Smoking (2x the risk!)
  • Unhealthy diets 
  • Lack of exercise (Don’t just watch sports, get out there!) 🤽🏽‍♀️🤾🏻‍♂️🚴‍♂️
  • Bad sleeping habits 
  • Excessive alcohol consumption 

Anxiety and stress

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

Diabetes and Alzheimer’s

According to the Alzheimer’s Association, people with diabetes endure a higher risk of Alzheimer’s, although the cause is not completely understood. 

What Drives Alzheimer's Progression?

People living with Alzheimer’s have both plaques and tangles in the brain. However, the presence of either one does not warrant a diagnosis of Alzheimer’s.

The mere presence of plaques is not a definitive Alzheimer’s diagnosis.

Misfolded Synuclein and TDP-43 may also play a role in driving the disease progression.

Alzheimer's on a Molecular Level

Alzheimer’s causes widespread damage in the cerebral cortex compared to other brain diseases. 

High levels of misfolded Abeta in spinal fluid spread the disease extracellularly from cell to cell. 

Misfolded Tau causes direct brain damage, leading to cognitive and motor decline. Specifically,

  • Tau prions appear prominently in the brain regions where maximum cell loss occurs, causing the brain to shrink in severe cases.

  • Tau tangles, alone, cause progressive cognitive and motor damage to the brain in non-Alzheimer’s dementia.

  • Plaques, alone, frequently appear in elderly individuals without signs of dementia or cognitive decline.

Tauopathy

Tau tangles alone appear sufficient to cause a progressive brain disease called Tauopathy. It causes localized damage in one or two regions of the brain.

How is Alzheimer's Diagnosed?

Currently, it’s diagnosed based on symptoms. When individuals experience memory loss, for example, they visit the doctor’s office for tests.

According to the National Institute of Aging, presently, there are no tests that can definitively diagnose Alzheimer’s until an autopsy.

During the early stages, doctors rely on several diagnosing methods:

  • Machine-learning algorithms
  • Speech pattern analysis, and
  • Sensors to diagnose speech and movement symptoms

These sensors 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

Alzheimer’s diagnosis relies primarily on cognitive symptom observations.

PET/MRI Scans

Doctors employ PET/MRI scanning to detect plaques and tangles. First, radioactive tracers specific for Abeta or Tau prions are injected into the patient’s body. Brain imaging immediately follows.

MRI scans reveal early structural damage to the brain. In some cases, damage to blood vessels and the blood-brain barrier are shown.

PET/MRI scans run about $5,000 and $2,500, respectively. If the results reveal plaques and tangles, it’s costly confirmation that irreversible brain damage has already occured.

Alzheimer's 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 misfolded proteins make up the enemy force. Until now, science has only been able to identify these bad guys by autopsy. Our first breakthrough SYNTap Biomarker Test™️ identifies misfolded Synuclein, a critical biomarker differentiating Alzheimer’s from LBD.
This pivotal achievement sets up a final mission – Detect the remaining rogue agents, and push onwards to victory: A CURE.
We’re working hard to roll out the other three biomarker tests in the near future.

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

lewy body dementia

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

Misdiagnosis

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

Plaques alone are inconclusive for an Alzheimer’s diagnosis.

Consider these statistics:

  • 20% of healthy people aged 80+ have plaques but no dementia.
  • 20% of people with dementia have no plaques.

Biomarker testing aims squarely to STOP the rampant Alzheimer’s misdiagnosis. Knowledge is power. 

Treatments

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 detecting early. 

Why early detect when there’s no cure? 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?

Doctors were finally able to detect and analyze cancer in the early stages. Early detection is key. Researchers 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 testing leads to cures.

Our vision:
A world without Alzheimer’s

Biomarker testing empowers personalized medicine. 

This is the nexus to the cure!

We innovate biomarker-targeted drugs, matching the right patients to the right treatment.

alzheimer's biomarker profile

Our vision:
A world without Alzheimer’s

Biomarker testing empowers personalized medicine. 

This is the nexus to the cure!

We innovate biomarker-targeted drugs, matching the right patients to the right treatment.

Alzheimer's Early Onset

Early-onset is relatively rare, experienced by about 5% of patients.

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

Also, people carrying the ApoE4 gene tend to have an earlier onset.

Power of Early Prevention

According to the Alzheimer’s Association, delaying symptom onset by just 5 years could reduce the patient pool by as much as 42%!

delay onset of alzheimer's

Power of Early Prevention

According to the Alzheimer’s Association, delaying symptom onset by just 5 years could reduce the patient pool by as much as 42%!

Lifestyle Changes to Delay Onset

  1. Exercise regularly ⛷🚴‍♀️🏋🏽‍♂️
  2. A healthy diet (eat those broccoli florets!)
  3. Stop smoking 
  4. Maintain social activities
  5. Keep intellectually engaged through reading (like this page)
  6. Develop a fun new hobby (camel-racing, anybody?) 🐫  
  7. Maintain emotional and mental health 😇

Is Alzheimer's Hereditary?

Alzheimer’s is mainly a sporadic disease, meaning genetics may increase the risk but are not the determining factors.

Hereditary cases are relatively rare, involving mutations in the Abeta gene. This leads to an increased risk of Abeta misfolding. In addition, certain normal gene variants, such as ApoE4, may increase the risk. 

People with either one or two copies of ApoE4 have a 3-10X increased risk.

Nevertheless, not all people with ApoE4 develop the disease. Conversely, many Alzheimer’s patients do not carry ApoE4.

FAQs

It's transmitted like a virus between connected nerve cells. As each cell is affected, it is irreversibly damaged.

Over time, the progressive loss of neurons affects memory and executive function. In the late stages, the brain accumulates large clusters of both plaques and tangles.

This leads to actual shrinkage of the brain, detectable by MRI imaging. This is confirmed through visual analysis, the weight of the brain post-mortem, and microscopic inspection.

Alzheimer's is currently the sixth-leading cause of death in the US. It takes an estimated 100,000 lives per year.

The disease shortens lifespan directly through damage to critical pathways in the brain. Indirectly, it reduces lifespan by robbing our ability to care for ourselves. 

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