Some friends and I are talking about our favorite foods. “What’s yours?” one asks me. I can feel the answer just outside the horizon of my consciousness, but out of my reach. My heart starts beating; I feel dizzy.
Anyone over the age of 50 has probably experienced some version of this challenge, euphemistically called “the big moment.” The more often it happens, the greater the fear. Anxiety is widespread. Among neurocognitive disorders, none are more prevalent in the general population imagination than Alzheimer’s disease. Recent estimates suggest it may be the third leading cause of death among adults in North America, behind heart disease and cancer.
Twenty years ago, an extensive paper was cited in the journal Nature Alzheimer’s is caused by the accumulation of abnormal proteins, particularly sticky beta-amyloid, that accumulates outside neurons and tangles of tau, or misfolded proteins, into plaques. Together, they disrupt cell communication and cause cell death.
For the past two decades, the amyloid hypothesis has dominated the field, guiding countless clinical trials and drug development programs. However, the results were disappointing. Despite many efforts, progress in prevention and treatment has been minimal. Increasingly, researchers are exploring alternative explanations, new ways of thinking about a disease that is uncooperative to understand.
According to some estimates, 40 percent dementia conditions (including Alzheimer’s disease) worldwide are associated with risk factors that can be modified at least during one’s lifetime. Exploring these modifiable factors and what practical steps we can take to support healthy brain aging will be the subject of my next article. Today we will look at the latest research on the biology and diagnosis of this condition.
An Appetite for Energy
A new area of research concerns the brain’s strange appetite for energy. Every thought, every one memoryto fire and communicate with neurons, a process fueled by ATP, or adenosine triphosphate, the primary molecule for storing and transporting energy in all living cells. It supports important processes such as muscle contraction, nerve impulses and chemical synthesis. ATP is produced by mitochondriamicroscopic power plants inside our cells. When mitochondrial function declines, neurons struggle to meet their energy needs.
Interesting experiments with fruit flies and mice show that increasing mitochondrial energy production can improve memory formation. Animals given the increased metabolism were able to form long-term memories after a single encounter with the stimulus for more than 24 hours, bypassing the usual need for repeated learning. The findings suggest that even small improvements in cellular energy supply can have an impact on the consolidation of memories, potentially with obvious relevance to Alzheimer’s disease.
Researchers at the University of Porto in Portugal are investigating treatments aimed at restoring mitochondrial health. Proposed strategies include targeted antioxidants, drugs that stimulate mitochondrial biogenesis, and compounds that stabilize mitochondrial dynamics. By preserving the cellular energy machinery, such therapies may slow or reverse the course of neurodegenerative disease.
Alzheimer’s research has traditionally focused on immune activity in the brain itself, particularly among resident immune cells such as microglia. Immune cells appear outside the brain and enter the cerebrospinal fluid in Alzheimer’s patients, Northwestern University researchers report. The reason this is so important is that it will help expand 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 disease.
Complex work
The diagnosis of Alzheimer’s disease remains a complex task. Clinicians rely on careful history taking, cognitive testing, laboratory work, and increasingly sophisticated imaging techniques. These include magnetic resonance imaging, which can reveal shrinkage in the hippocampus, a brain structure important for memory and often one of the first areas affected. Specialized and expensive positron emission tomography scans can detect amyloid plaques or tau deposits, which provide early detection of brain pathology. In some cases, doctors may also analyze cerebrospinal fluid obtained through a lumbar puncture.
In May 2025, the US Food and Drug Administration approved the first blood test designed to detect biomarkers Alzheimer’s-related, designed for people age 55 and older who are showing signs of cognitive decline. The test measures a specific phosphorylated tau protein (pTau217) and amyloid-beta ratio to detect Alzheimer’s-related brain changes and offers a less invasive alternative to PET scans or spinal taps. Clinical studies have shown that a positive result has a high correlation (more than 90 percent) with the presence of amyloid plaque, while a negative result can help rule out the disease. It is used by doctors in conjunction with other clinical assessments, not as a stand-alone test.
In the coming years, there will be more studies that will surely bring us closer to reliable early diagnosis.
However, a word of caution. Early diagnosis is not a boon. A study that one has mild cognitive impairment associated with Alzheimer’s disease can be both calming and disturbing. Some people welcome knowledge. It allows them to make financial agreements, advance care directives and have conversations with family members that might have been avoided for a long time. Others find the data troubling, especially given the lack of definitive treatment.
Also, diagnosis, even at this age AIis just an informed guess. Two people with almost identical brain scans can look completely different in everyday life. Educationcognitive resources, social networks, and the presence of other medical conditions all determine the pattern of symptoms. The body, especially the brain, maintains a state of wonder even under siege stability.
As Yogi Berra once said, “Predictions are difficult, especially about the future.”
