A recent study reported in the scientific journal Nature suggested that a deficiency of lithium in the brain may play an important role in causing Alzheimer’s disease.¹ This finding is particularly interesting because lithium is not generally considered to be an essential nutrient, although it has long been suspected to be neuroprotective.² The results of the new study suggest that providing lithium supplementation in a form that does not get bound up in the amyloid plaques in the brain might be useful for preventing and even treating this devastating disease. This finding aligns with the results of an earlier study, which showed a lower risk of dementia in areas that had moderate amounts of lithium in the drinking water.³ A case-control study from Denmark likewise showed that people who had moderate amounts of lithium in their drinking water were less likely to get dementia.⁴ However, many Americans live in areas where there is remarkably little lithium in the drinking-water sources (Figure 1).⁵

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This news about lithium is exciting. However, those of us who know how scientific research gets funded and scientific findings get disseminated realize that there’s still a lot of work to do. The problem is that nobody will get rich from this finding. For this reason, no major corporation will have a financial incentive to do the necessary follow-up research. Thus, it will be up to the federal government to do this research—at a time when federal research budgets have been slashed for partisan ideological reasons. Nor will any company fund a huge advertising campaign to alert doctors and the public to this information.

What can Mensans do about this?

I suggest that members of American Mensa create a Dementia Research special interest group (SIG). Its membership should include people with expertise in relevant disciplines (e.g., neuroscience, pharmacology, toxicology, clinical research, healthcare economics, medical informatics) to comb through the published literature, generate evidence-based reviews of currently available interventions, and recommend studies to fill in the gaps of current knowledge. If we are really clever, we might even find ways to raise the money for someone to do some of those studies.

Why should Mensans do this? The reason is simple. Each of us has a brain, and so do all of our friends and relations. Thus, any of us can go on to suffer from Alzheimer’s disease. To pursue this research would be an act of self-defense. As the Royal Navy’s traditional toast for Wednesdays puts it:

To ourselves (“as no-one else is likely to concern themselves with our welfare”)

What is Alzheimer’s disease?

Alzheimer’s disease is a brain disorder that is a common cause of senile dementia (loss of memory and thinking skills in old age). It was named after Alois Alzheimer, who was a German psychiatrist and neuropathologist (i.e., someone who studies brain tissue). In the late 19^th century, French and German neuropathologists began doing autopsies of people who had suffered from mental or neurological problems. These neuropathologists tried to relate the autopsy findings (brain abnormalities) with the disorders the patients had before death. This approach is called the clinicopathological method.

In 1901, a woman named Auguste Deter was brought to the city asylum in Frankfurt, Germany, because of odd behavior and a loss of short-term memory.⁶ No treatment seemed to be effective. Sadly, her condition got steadily worse. She died in 1906. During her autopsy, Alzheimer took samples of her brain tissue. He used a new staining technique (Bielschowsky silver stain) to make her nerve cells visible under the microscope. He then found that her brain tissue was peppered with abnormal structures (plaques and tangles) that no one had seen before. We now know that the plaques, which are found between cells, are made of a protein fragment called amyloid beta (β-amyloid). The tangles, which formed inside cells, are made up of an abnormally phosphorylated protein called tau.

How is Alzheimer’s disease diagnosed?

For decades, the diagnosis of Alzheimer’s disease could be made only at autopsy, when the plaques and tangles could be seen in specimens of brain tissue. However, doctors eventually learned to make an accurate presumptive diagnosis while the patient was still alive. A presumptive diagnosis is an educated guess based on the known probability of something that can be confirmed later. Today, the presumptive diagnosis of Alzheimer’s disease is highly accurate because it is based on biomarkers.⁷ These include tests for fragments of β-amyloid protein or tau protein in blood or spinal fluid and positron emission tomography (PET) imaging with radiotracers that bind to β-amyloid or tau in the brain. Yet the results of these tests can be hard to interpret.

The Jack hypothesis is that the various biomarker tests for Alzheimer’s disease start showing abnormal results in a predictable order⁸:

1. Fragments of β-amyloid protein appear in cerebrospinal fluid.
2. Amyloid plaques can be visualized in the brain by PET scans.
3. Tau protein can be found in cerebrospinal fluid
4. Magnetic resonance imaging (MRI) shows degeneration of brain tissue and PET scans with glucose tagged with positron-emitting fluorine-18 shows abnormal glucose metabolism in brain tissue.
5. The patient starts showing signs of minimal cognitive impairment, which may progress to dementia. 

The Jack hypothesis suggests that Alzheimer’s disease may result from a cascade of problems: one problem triggering another problem, which triggers another problem. This raises important questions. Which of these biomarkers are causes of the problem, and which ones are merely markers of the problem? Can something be done to stop the cascade, before the dementia starts?

What are the amyloid plaques in Alzheimer’s disease made of?

The term amyloid is used in medicine to refer to the shape of a protein, not the kind of protein involved. All proteins consist of strings of amino acids. The order of those amino acids, which is unique to each protein, is called the primary structure of the protein. Yet various portions of that string of amino acids can take on a shape, called its secondary structure (Figure 2). Examples include a corkscrew shape (a helix) or a zigzag shape that forms a pleated sheet (β-sheet). An amyloid consists of layers of β-sheet that build up to form a fibrillar (fiber-like) shape. There are some natural amyloid proteins (e.g., in spider silk). However, the abnormal buildup of an amyloid protein in tissue is called amyloidosis. Alzheimer’s disease involves just one form of amyloidosis.

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The protein in the amyloid plaques in Alzheimer’s disease came originally from β-amyloid precursor protein (AβPP, encoded by the gene APP). AβPP is a normal part of healthy cell membranes, and a lot of it is found in the synapses (gaps between nerve cells). AβPP probably plays an important role in the formation and repair of the synapse. Similar versions of AβPP are found in all mammals, and a related protein has even been found in fruit flies. Mice that lack the APP gene have severe metabolic problems and behavioral deficits.⁹

AβPP can be broken down into β-amyloid, which consists of strings of 37 to 49 amino acid residues.¹⁰ The amount of β-amyloid in the brain depends on the rate of production as well as the rates of destruction and elimination of β-amyloid. Within the brain, β-amyloid can be broken down by protease enzymes,¹¹ or it can simply be drained from the brain through the glymphatic system. The glymphatic system is a recently discovered drainage system that is particularly active during sleep.¹² 

β-Amyloid might have some useful functions. It might help to protect the brain against oxidative stress, regulate the transport of cholesterol, and even fight infections, by promoting inflammation. This raises an interesting question: Is an overload of β-amyloid in the brain the cause of Alzheimer’s disease? Or is the amyloid a result of the disease process? Or is the amyloid a result that then contributes to the disease process? The answer is not yet clear.

What are the tangles in Alzheimer’s disease made of?

Tau proteins are small proteins that are found within cells. (Tau stands for tubulin associated unit.) Tubulins are proteins that make up the microtubules within the cell. The microtubules form part of the cell’s cytoskeleton (its underlying structure) and also help to transport substances within the cell. Thus, tau proteins are necessary for the normal structure and function of a cell.

Tau proteins are phosphoproteins, which means that they have binding sites for phosphate groups. The addition of the phosphate groups to these binding sites is regulated by kinase and phosphatase enzymes. Unfortunately, tau can sometimes become hyperphosphorylated (i.e., with too many phosphate groups or a phosphate group at an unfortunate site), sometimes as a result of oxidative stress.¹³ The abnormal tau may then take on an abnormal shape (misfolding). The abnormal tau breaks free from the microtubules and can clump together into groups of two (dimers) or three (trimers). These dimers and trimers can clump into larger aggregates called neurofibrillary tangles (NFTs).¹⁴ The breakdown of the microtubules and the buildup of the NFTs can disrupt the structure and function of the cell, possibly leading to cell death. Oligomers (dimers and trimers) of abnormal tau might even spread to other cells, causing misfolding of their native tau proteins.¹⁵ The disorders that result from abnormal aggregation of tau protein in neurons are called tauopathies.

Alzheimer’s disease is classified as a tauopathy because of the NFTs. However, there are several tauopathies that do not feature amyloid plaques. So, the relationship between amyloid and tau is unclear.

Is Alzheimer’s disease genetic?

Alzheimer’s disease occurs only in human beings. This suggests that the disease is at least partly genetic. In fact, the early-onset cases tend to run in families because they are linked to a single dangerous gene.¹⁶ However, there are other genes that increase or decrease one’s risk of getting Alzheimer’s disease. One study identified 133 gene variants that seem to influence the risk of Alzheimer’s disease.¹⁷ Here are some of the most commonly implicated genes:

• APOE—This is the gene for apolipoprotein E, which is a protein involved in the transport of fats, cholesterol, and fat-soluble vitamins in the bloodstream. Everyone has two copies of this gene, one from their mother, and the other from their father. People with two copies of the ε4 allele of this gene are at increased risk of Alzheimer’s disease. People with two copies of the ε2 allele have a reduced risk of Alzheimer’s disease.
• Presenilin genes—Mutations in the gene for presenilin 1 (PSEN1, found on chromosome 14) or presenilin 2 (PSEN2, found on chromosome 1) are associated with familial, early-onset Alzheimer’s disease.
• APP—Mutations in the gene for AβPP can increase the risk of Alzheimer’s disease.

Preserved tissue samples from Auguste Deter (Alois Alzheimer’s original patient) underwent genetic testing more than a century after her death. The testing showed that she had a mutation in PSEN1, which was undoubtedly the cause of her illness.¹⁸ Surprisingly, her mutation was one that had not yet been identified.

How can Alzheimer’s disease be prevented or treated?

Even if your genetics put you in a higher risk category, you might be able to delay or even prevent the onset of dementia, through lifestyle choices and even some medications and cheap dietary supplements that are already on the market.

• Many companies are already marketing low-dose lithium supplements.
• A low-fat, plant-based diet improved cognitive function in people with mild cognitive impairment or early dementia.¹⁹ The effects may be due partly to improved blood flow (because of a decrease in serum cholesterol) and partly to a decrease in oxidative stress and inflammation.
• Exercise seems to have preventive effects on Alzheimer’s disease.²⁰
• The yellow spice turmeric, which is known to block TNF, may also be useful in preventing Alzheimer’s disease.²¹
• Benfotiamine, which is a fat-soluble form of thiamine (vitamin B1) may help to prevent senile dementia.²² This vitamin, which is cheap and already on the market, has a long history of safe use.
• Photobiomodulation (red light therapy) is a safe treatment that may provide significant improvement in cognitive function in dementia patients.²³
• Light that flickers at a frequency of 40 Hz induced brainwaves in the gamma frequency and may have numerous benefits for brain health.²⁴
• The use of medication to block tumor necrosis factor (TNF) could prevent or even arrest Alzheimer’s disease, especially if it is given through the perispinal route.²⁵

As you can see, these are interventions that are already available, often without a prescription, and most of them are cheap. Yet the word about the value of these available treatments is not being widely shared. We have our work cut out for us.

References

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16.        Yokomizo M, Sadek M, Williams E, et al. A unique subpopulation of wild-type neurons recapitulating familial Alzheimer’s disease phenotypes. Cell Death Dis. Aug 9 2025;16(1):604. doi:10.1038/s41419-025-07934-0

17.        Khani M, Akçimen F, Grant SM, et al. Biobank-scale genetic characterization of Alzheimer’s disease and related dementias across diverse ancestries. Nature Communications. 2025/08/14 2025;16(1):7554. doi:10.1038/s41467-025-62108-y

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