Proteins Linked to Alzheimer’s Disease Now Observable in Real Time

According to the Alzheimer’s Association, nearly 7 million Americans are currently diagnosed with Alzheimer’s disease, the most common type of dementia. Furthermore, the situation is expected to worsen — by 2050, around 13 million Americans are projected to be diagnosed with this neurodegenerative disease.¹

Alzheimer’s disease remains challenging for modern medicine to diagnose and treat. However, a recent study² has made a breakthrough in understanding how the disease progresses, creating a foundation for future clinicians and researchers to build upon to create better treatment plans.

A Breakthrough in Observing Alzheimer’s Disease Progression

In a study³ published in Science Advances, researchers were able to visualize the development of amyloid-beta proteins to see how Alzheimer’s disease spreads. Beta-amyloid proteins have been observed using a variety of methods, several of which were reviewed in the study:

“Methodological advances have been able to resolve the ultrastructure of Aβ and tau protein aggregates formed along the primary nucleation pathway using cryo-electron microscopy (cryo-EM) and solid-state nuclear magnetic resonance spectroscopy.

Likewise, the aggregation kinetics and toxicity of these proteins have been investigated using ultrasensitive fluorescence-based assays, nanopore devices, and circular dichroism.

Details on the morphology, on-surface assembly, and chemical structure of Aβ and tau protein aggregates have also been made accessible using standard atomic force microscopy (AFM), video-rate AFM, and infrared spectroscopy.”

For context, beta-amyloid proteins aggregate in the brain, and they’re suspected of playing a key role in the development of Alzheimer’s. Hence, they’re what researchers usually focus on to find therapeutic solutions.⁴ Previous staining methods used for observational analysis distort the protein structures.

To find new ways to analyze the mechanisms of Alzheimer’s disease, the team used liquid-based atomic force microscopy (AFM). As explained by the authors:⁵

“Building on the observations from previous secondary nucleation studies, we postulated that it should be feasible with a high-resolution AFM to record elementary information such as oligomer size, shape, and adsorption site on individual fibrils with sub-10-nm diameter. Operating the AFM in an aqueous solution medium would allow the diffusion of oligomers on the fibril surface.”

Tracking the Progression of Alzheimer’s Disease in Real Time

Once the team settled on the methodology, they moved onto testing. To start, they agitated beta-amyloid samples for 30 minutes at room temperature. Then, they set up different experiments to observe the growth and progression protein aggregates from 30 seconds to 250 hours:⁶

“Nanoscale imaging supported by atomic-scale molecular simulations tracked the adsorption and proliferation of oligomeric assemblies at nonperiodically spaced catalytic sites on the fibril surface. Upon confirming that fibril edges are preferential binding sites for oligomers during embryonic stages, the secondary fibrillar size changes were quantified during the growth stages.”

From their observations of protein fibril development in real time, they were able to classify some of them as “superspreaders” based on their surface anatomy. Specifically, these superspreaders “feature highly active edges and surfaces where new protein molecules accumulate, eventually forming longer fibrils that may spread across brain tissue.”

As they spread, more protein aggregation occurs, effectively progressing the hallmarks of Alzheimer’s disease. Ultimately, the research team hopes that this breakthrough in fibril analysis will be able to help improve the diagnosis and monitoring of neurodegenerative diseases. “This work brings us another step closer to better understanding how these proteins spread in brain tissue of Alzheimer’s disease,” says Peter Nirmalraj, one of the authors of the study.⁷

Mitochondrial Dysfunction Is at the Heart of Alzheimer’s Disease

As researchers continue to come up with new tools to help diagnose and treat Alzheimer’s better, following a healthy lifestyle is important to reduce your risk. Prevention is by far your best option. I believe addressing mitochondrial dysfunction is key to protecting cognitive function, which is achieved by improving your cellular health.

The first thing to address is your diet. A study published in Neurology noted that eating an inflammatory diet raises your risk of dementia.⁸ In addition, I believe that there are three major toxins damaging your mitochondrial function by affecting intracellular calcium, which subsequently impacts cellular health.

Essentially, when calcium within your cells increase, your body produces superoxide and nitric oxide. These two combine to form peroxynitrite, a potent reactive oxygen species that contributes to poor health. Three pervasive toxins that raise intracellular calcium levels and drive peroxynitrite formation include:

Keep Your Gut Flora Healthy to Protect Cognitive Function

Your gut microbiome is one of the most crucial aspects for achieving optimal health. Research¹¹ has shown that it plays a role in various functions, such as modulating the immune system, glucose metabolism and reducing insulin resistance. In addition to these findings, a study¹² published in Scientific Reports showed that certain bacterial strains in the gut increased the risk of Alzheimer’s disease.

In the study, the researchers singled out strains such as Collinsella, Lachnospira and Veillonella as contributors to the risk of Alzheimer’s disease. According to the study authors:¹³

“In our analyses, Collinsella from the phylum Actinobacteria was identified as a risk factor for AD (Alzheimer’s disease) in both the discovery and replication samples … Importantly, an increased abundance of this genus has also been observed in AD transgenic mice and AD patients. Our findings provide evidence at the human genome-wide level of a connection between Collinsella and AD that supports previous observational studies …

In addition, we identified two Firmicutes genera as risk factors for AD (Lachnospira and Veillonella), with Veillonella being validated in the replication sample. Recently, it was reported that AD patients have an abundance of Veillonella in their oral microbiome. In the gut, it has been shown that an overabundance of species like V.parvula promotes intestinal inflammation …

The dual association of oral and gut abundance of Veillonella with disease points to this genus as a target for therapeutics and a potential bridge between conditions like gut inflammation and periodontitis with AD.”

The researchers also identified strains that provide protective benefits against Alzheimer’s disease, such as Eubacterium nodatum and Eisenbergiella. These produce short-chain fatty acids (SCFAs), particularly butyrate, from dietary carbohydrates.¹⁴

Butyrate nourishes your colonic epithelial cells, reinforcing the intestinal barrier. SCFAs also stimulate mucin production, creating a protective shield against harmful bacteria. Akkermansia also produces SCFAs, and research has shown that Alzheimer’s patients tend to have very low levels of this important keystone species.¹⁵

Carbohydrates Help Support Your Gut Health

Nurturing oxygen-intolerant beneficial bacteria, including Akkermansia, will strengthen your intestinal lining to create an environment that promotes overall wellness. On the other hand, low levels of oxygen-intolerant bacteria will lead to increased intestinal permeability, also known as leaky gut.

This causes openings in the intestinal barrier, allowing toxins, undigested food particles and harmful microbes to enter your bloodstream, resulting in systemic inflammation and chronic health issues.

To create an environment that allows your gut microbiome to thrive, increasing your intake of carbohydrates is a priority. Ashley Armstong provides some good recommendations for gut-friendly carbs, which include:

1. Well-cooked white rice
2. Sourdough bread
3. Root vegetables like potatoes and sweet potatoes
4. Fresh, ripe fruits
5. Masa harina, or traditionally made tortillas

Also remember to include fermented foods. I’m a big believer of making your own fermented vegetables at home because they’re both simple and cost-effective to prepare. I don’t recommend buying commercially prepared fermented vegetables, as they often contain artificial sweeteners and additives, negating the benefits of fermented foods in the first place.

Additional Strategies to Prevent Alzheimer’s Disease

Aside from optimizing your gut health and mitochondrial function, there’s a plethora of helpful Alzheimer’s prevention strategies, several of which are outlined below:

Avoid gluten and casein (primarily wheat and pasteurized dairy, but not dairy fat, such as butter) — As noted in a 2022 study,16 your blood-brain barrier is negatively affected by gluten. When bacteria enter your blood stream, the risk of Alzheimer’s disease increases. Other cognitive disorders are linked to a weakened blood-brain barrier as well, such as Parkinson’s disease, anxiety and depression.

Make sure you’re getting enough animal-based omega-3 fats — Omega-3 fats, namely EPA and DHA, help by preventing cell damage caused by Alzheimer’s disease, thereby slowing down its progression and lowering your risk of developing the disorder. That said, omega-3s are PUFAs, so don’t overdo it.

Optimize your vitamin D level with safe sun exposure — Strong links between low levels of vitamin D in Alzheimer’s patients and poor outcomes on cognitive tests have been revealed. In a 2023 study,17 increasing vitamin D reduced dementia risk by 40%. The best way to get vitamin D is through sensible sun exposure, aiming for a blood level between 60 ng/mL and 80 ng/mL. However, you need to purge seed oils from your body before going into the sun at solar noon. The LA in your skin oxidizes when exposed to sunlight, causing inflammation and skin damage. To protect your skin, avoid sun exposure during solar noon for four to six months as you work on removing LA from your body. Stick to sunlight during early morning and late afternoon in the meantime. For additional skin defense, your can take astaxanthin, a low-dose aspirin or molecular hydrogen. Niacinamide cream will also lower your risk of skin damage.

Keep your fasting insulin levels below 3 — Insulin resistance is linked to accelerated brain aging, as well as neurodegeneration.18

Eat a nutritious diet, rich in folate — Vegetables, without question, are your best form of folate. Avoid supplements like folic acid, which is the inferior synthetic version of folate. Research shows that folate is a protective factor against Alzheimer’s disease.19

Avoid and eliminate mercury and aluminum from your body — Dental amalgam fillings, which are 50% mercury by weight, are one of the major sources of heavy metal toxicity. Make sure you use a biological dentist to have your amalgams removed. Sources of aluminum include antiperspirants, nonstick cookware and vaccine adjuvants.

Make sure your iron isn’t elevated and donate blood if it is — A study20 published in Aging Medicine shows that excess iron increases your risk of Alzheimer’s disease by initiating the Fenton reaction, leading to increased oxidative stress.

Exercise regularly — Exercise triggers beneficial changes that support cognitive function. Particularly, it’s been shown to improve blood flow to the brain, leading to an increase in biomarkers related to improved neuronal plasticity and better cell survival.21

Eat blueberries and other antioxidant-rich foods — Wild blueberries, which have high anthocyanin and antioxidant content, are known to guard against neurological diseases.

Challenge your mind daily — Mental stimulation, such as learning to play a musical instrument, is associated with a decreased risk of Alzheimer’s.22

Avoid anticholinergics and statin drugs — Drugs that block acetylcholine, a nervous system neurotransmitter, have been shown to increase your risk of dementia. These drugs include certain nighttime pain relievers, antihistamines, sleep aids, certain antidepressants, medications to control incontinence and certain narcotic pain relievers. Statin drugs are particularly problematic because they suppress the synthesis of cholesterol, deplete your brain of CoQ10 and neurotransmitter precursors, and prevent adequate delivery of essential fatty acids and fat-soluble antioxidants to your brain by inhibiting the production of the indispensable carrier biomolecule known as low-density lipoprotein.