Decoding Alzheimer’s disease

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Thomas R. Verny is a clinical psychiatrist, academic, award-winning author, poet and public speaker. He is the author of eight books, including the global bestseller The Secret Life of the Unborn Child and The Embodied Mind: Understanding the Mysteries of Cellular Memory, Consciousness and Our Bodies.

Some friends and I are discussing our favourite dishes. “What’s yours?” one asks me. I can feel the answer, hovering just beyond the horizon of my consciousness but beyond my reach. My heart begins to pound; my head starts to spin. Then, suddenly, the words arrive. “Duck confit,” I exclaim, perhaps an octave higher than necessary. Instant relief, swiftly chased by angst. In my mind’s eye, a neon sign lights up: Alzheimer’s disease.

Anyone past the age of 50 has likely experienced a version of this predicament, euphemistically termed a “senior’s moment.” The more frequently it occurs, the more dread it triggers. The worry is widely shared. Among neurocognitive disorders, none looms larger in the public imagination than Alzheimer’s disease. Recent estimates suggest it may rank third after heart disease and cancer as a cause of death among older adults in North America.

Although this condition has existed since time immemorial, it was not recognized as a disease until 1906 when the neurologist Alois Alzheimer presented the case of a patient known as Auguste D at a meeting of German psychiatrists in Tübingen. She had become suspicious, forgetful, and increasingly disoriented before dying in her 50s. Alzheimer noted peculiar abnormalities in her brain, dense plaques and tangled fibres within nerve cells.

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One hundred years later, a widely cited paper in the journal Nature argued that Alzheimer’s is driven by the accumulation of abnormal proteins in the brain, specifically a sticky one called beta-amyloid that builds up into plaques outside of neurons and tau tangles, or misfolded proteins, within them. Together they disrupt cell communication and cause cell death. Plaques appear first, while tau directly correlates with cognitive decline and neuronal death. Importantly, the process appears to begin years, perhaps decades, before symptoms appear. [1]

For the last two decades the amyloid hypothesis has dominated the field, guiding countless clinical trials and drug-development programs. Yet the results have been disappointing. Despite enormous effort, progress in prevention and treatment has been modest at best. More recently, serious concerns have emerged regarding the integrity of some of the data underlying the amyloid hypothesis. [2] Increasingly, researchers are exploring alternative explanations, new ways of thinking about a disease that remains unco-operative to understanding.

My aim in this column is to acquaint the reader with recent advances in our understanding of the nature, diagnosis and treatment of Alzheimer’s. By some estimates 40 per cent of dementia cases (Alzheimer’s included) worldwide are linked to risk factors that can, at least in principle, be modified over the course of one’s life. [3] Exploring these modifiable factors and what practical steps we can take to support healthy brain aging will be the subjects of my May column.

One novel direction of research comes from the lab of Donald Weaver at the University of Toronto. Dr. Weaver has suggested that Alzheimer’s may not primarily be a brain disease at all, but rather an autoimmune disorder. Certain fat molecules found in bacterial membranes closely resemble those in the membranes of brain cells. Beta-amyloid, he proposes, may function as part of the brain’s immune defence. In attempting to attack invading microbes, it may mistakenly target the brain’s own cells, setting off a slow cascade of damage that eventually manifests as dementia. [4]

If this theory proves correct, treatments already used in other autoimmune diseases, conditions such as celiac disease, Crohn’s disease, Type-1 diabetes, eczema, or multiple sclerosis, might some day prove beneficial in treating Alzheimer’s as well.

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Another line of inquiry concerns the brain’s remarkable appetite for energy. Each thought, each memory, requires neurons to fire and communicate, a process fuelled by ATP, or adenosine triphosphate, the primary molecule for storing and transferring energy in all living cells. It powers essential processes like muscle contraction, nerve impulses, and chemical synthesis. ATP is generated by mitochondria, the microscopic power plants inside our cells. When mitochondrial function falters, neurons struggle to meet their energy demands.

Intriguing experiments with fruit flies and mice suggest that enhancing mitochondrial energy production can improve memory formation. Animals given a metabolic boost were able to form long-term memories lasting more than 24 hours after a single encounter with a stimulus, bypassing the usual need for repeated training. [5] The findings hint that even modest improvements in cellular energy supply could influence how memories are consolidated, a prospect of obvious relevance for Alzheimer’s.

Researchers such as Daniela Mendes at the University of Porto in Portugal are investigating therapies aimed at restoring mitochondrial health. Proposed strategies include targeted antioxidants, drugs that stimulate mitochondrial biogenesis, and compounds that stabilize mitochondrial dynamics. By preserving the cell’s energy machinery, such treatments might slow or perhaps modify the course of neurodegenerative disease. [6]

Meanwhile, another cellular player has stepped into the spotlight: microglia. These immune cells patrol the brain, clearing debris and helping maintain brain health. However, research led by scientists at the University of Washington State suggests that rather than supporting neural cells, some microglia may overreact, damaging surrounding neurons by triggering inflammation. [7]

Investigators at Charles University in the Czech Republic have found unusually high iron deposits in dysfunctional microglia, sometimes accompanied by iron-laden macrophages and astrocytes. Macrophages and astrocytes act as the first line of defence to detect, engulf, and destroy foreign antigens, cellular debris, and dead cells. The findings point toward inflammatory processes and disruptions in the blood-brain barrier, raising the possibility that regulating iron levels might prove therapeutically useful. [8]

The high-voltage quest to fix the errant mind

Alzheimer’s research has traditionally focused on immune activity within the brain itself, particularly among resident immune cells such as microglia. Now, researchers at Northwestern University found that the body’s broader immune system may also be involved. All the major categories of white blood cells examined in Alzheimer’s patients displayed some degree of modification.

A surprise finding of this study involved a subset of immune cells called CD8 T-cells. In patients with Alzheimer’s, these cells displayed increased visibility of a membrane receptor known as CXCR3, which acts like a homing signal, guiding them toward sites of inflammation, including the brain. This is intriguing, because T- cells are usually kept at arm’s length from the brain, where their presence can sometimes do more harm than good.

The Northwestern research demonstrates that immune cells originating outside the brain expand and enter the cerebrospinal fluid in patients with Alzheimer’s. The reason that this is so significant is that it helps broaden the focus of research beyond brain-resident immune cells such as microglia to include systemic immune cells and provide new therapeutic targets in the treatment of the disease. [9, 10]

Even seemingly mundane biochemical processes may play a role. Studies at the University of Colorado indicate that normal aging reduces levels of nitric oxide in the body. The resulting decline in protein nitrosation appears to impair memory and learning. If researchers can find ways to halt or prevent the loss of nitrogen or replenish it they may open a promising avenue for slowing cognitive decline. [11]

Diagnosing Alzheimer’s disease remains a complicated undertaking, in part because several conditions can affect cognition simultaneously. The goal is to distinguish the disease from other, potentially treatable causes of cognitive impairment.

Clinicians rely on taking a careful clinical history, cognitive testing, laboratory work and increasingly sophisticated imaging techniques. These include magnetic resonance imaging (MRI) that can reveal shrinkage in the hippocampus, the brain structure crucial for memory and often one of the earliest regions affected. Positron emission tomography (PET) scans, more specialized and expensive, can detect amyloid plaques or tau deposits, providing an early glimpse of brain pathology. In some cases, physicians may also analyze cerebrospinal fluid obtained through a lumbar puncture.

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In May, 2025, the field took a notable step forward when the U.S. Food and Drug Administration approved the first blood test designed to detect biomarkers associated with Alzheimer’s, intended for people aged 55 or older who show signs of cognitive decline. The test measures specific phosphorylated tau protein (pTau217) and amyloid-beta ratio to detect Alzheimer’s-related brain changes, offering a less invasive alternative to PET scans or lumbar punctures. Clinical studies demonstrated that a positive result has a high correlation (over 90 per cent) with amyloid plaque presence, while a negative result can help rule out the disease. It is intended to be used by physicians in conjunction with other clinical assessments, not as a standalone test. [12]

The pTau217 + amyloid ratio blood tests are currently classified as “uninsured” in Canada. Major organizations (e.g., Alzheimer’s Association) released clinical practice guidelines (2025) supporting their use in specialist settings. They can be accessed via private labs with a doctor’s order. Some private insurers may reimburse.

PET scans and cerebrospinal fluid tests remain the “gold standard” in Canada. PET scans are expensive (for the government) and have long waiting lists. And how many people do you know who are keen on having a spinal tap? These tests are viewed by doctors for now as adjuncts, not standalone diagnostics.

Researchers at Houston Methodist are looking for early warning signs not in the brain but in the eyes. Studies suggest that subtle changes in the outer retina, particularly in its peripheral regions, may signal Alzheimer’s pathology long before symptoms appear. According to biomedical engineer Stephen Wong, these retinal alterations may precede disruptions in the brain’s “plumbing,” its network of fluid-clearing pathways. If confirmed, routine eye examinations might one day provide an early and non-invasive way to detect the disease years before memory loss becomes evident. [13]

In the coming years there will be more research that will surely bring us closer to a reliable early diagnosis.

The complex crisis facing men today

However, a word of warning. Early diagnosis is not an unalloyed blessing. Learning that one has mild cognitive impairment associated with Alzheimer’s disease can be both calming and unsettling. Some people welcome the knowledge. It allows them to make financial arrangements, advance directives regarding care, conversations with family members that may have been long avoided. Others find the information troubling, especially given the absence of a definitive cure.

Also, diagnosis, even in this age of AI, remains a cocktail of equal parts art and science with a dash of tact. Two individuals with nearly identical brain scans may function quite differently in everyday life. Education, cognitive reserve, social networks, and the presence of other medical conditions all shape how symptoms unfold. The body, especially the brain, even when under siege, retains an astonishing resilience.

As Yogi Berra once said, “It’s tough to make predictions, especially about the future.”

References

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3. Livingston, G., Huntley, J., Banerjee, S., … Mukadam, N. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet,396 (10248), 413–446.
4. Weaver, Donald. (2024). Alzheimer’s Might Not Actually Be a Brain Disease, Expert Reveals. The Conversation.
5. Vishwanath, A. A., Comyn, T., Sivakumar, R., ... de Juan-Sanz, J. (2024). Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory across species. bioRxiv, 2024-02.
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12. U.S. Food and Drug Administration. (2025). FDA clears first blood test used in diagnosing Alzheimer’s disease.
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