Some friends and I are discussing our favorite dishes. “What’s yours?” one asks me. I can feel the answer, hovering just beyond the horizon of my consciousness, but out of my reach. My heart begins to pound; my head starts to spin.
Anyone past the age of 50 has likely experienced a version of this predicament, euphemistically termed a “senior 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.
Twenty years ago, a widely cited paper in the journal Nature argued that Alzheimer’s is driven by the accumulation of abnormal proteins, specifically sticky 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.
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. Increasingly, researchers are exploring alternative explanations, new ways of thinking about a disease that remains uncooperative to understanding.
By some estimates, 40 percent 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. Exploring these modifiable factors and what practical steps we can take to support healthy brain aging will be the subject of my next post. Today, we shall look at the most recent research on the biology and diagnosis of this condition.
An Appetite for Energy
One novel direction of research concerns the brain’s remarkable appetite for energy. Each thought, each memory, requires neurons to fire and communicate, a process fueled 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. 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 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.
Alzheimer’s research has traditionally focused on immune activity within the brain itself, particularly among resident immune cells such as microglia. Researchers at Northwestern University report 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.
A Complicated Undertaking
Diagnosing Alzheimer’s disease remains a complicated undertaking. Clinicians rely on taking a careful clinical history, cognitive testing, laboratory work, and increasingly sophisticated imaging techniques. These include magnetic resonance imaging, which can reveal shrinkage in the hippocampus, the brain structure crucial for memory and often one of the earliest regions affected. Positron emission tomography 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.
In May 2025, 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.
In the coming years, there will be more research that will surely bring us closer to a reliable early diagnosis.
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, and 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, is only an informed guess. 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.”
