Building the Foundation for Earlier Alzheimer Disease Diagnosis

Alzheimer disease (AD) begins long before patients develop recognizable cognitive symptoms. Mounting evidence has shown that the biological changes underlying the disease, particularly amyloid accumulation followed by tau pathology, can precede clinical impairment by decades, creating an important opportunity for earlier diagnosis and intervention. As disease-modifying therapies continue to emerge, identifying individuals during these preclinical and prodromal stages has become one of the field's most pressing priorities.

At the 2026 Alzheimer's Association International Conference (AAIC), investigators presented findings from the analysis, "Blood Biomarker Assays Demonstrate Strong Rule-In Performance for Identifying Cognitively Unimpaired Alzheimer's Disease," which evaluated the performance of P-tau217 blood-based assays in cognitively unimpaired individuals against amyloid PET imaging. The study demonstrated strong positive predictive value and noninferior performance relative to amyloid PET, supporting the growing role of blood-based biomarkers as scalable tools for identifying underlying AD pathology and selecting patients who may benefit from earlier intervention strategies.

In this NeurologyLive^® Special Report, Yogesh Shah, MD, MPH, FAAFP, medical director of the Broadlawns Memory Clinic, site principal investigator for the University of Iowa Geriatric Workforce Empowerment Program, and board member of the Iowa Chapter of the Alzheimer's Association, begins by reviewing the biological cascade of AD. Shah explains how amyloid and tau drive disease progression, distinguishes mild cognitive impairment from dementia, and discusses how blood-based P-tau217 testing is already helping clinicians evaluate patients with objective cognitive impairment while highlighting its current indications and limitations.

Transcript edited for clarity.

Yogesh Shah, MD, MPH, FAAFP: As your listeners might know, Alzheimer's dementia falls under the broader umbrella of dementia, and Alzheimer's disease is one of the most common causes of dementia. With each type of dementia, we're learning that specific protein changes occur in the brain years before clinical symptoms develop.

In Alzheimer's disease, a protein called amyloid begins accumulating in the brain 15 to 20 years before symptoms appear. That amyloid accumulation eventually leads to another protein, tau. Tau contributes to brain cell death, which results in the earliest memory changes. That stage is known as mild cognitive impairment, or MCI, and it can eventually progress to dementia.

The difference between MCI and dementia is that patients with MCI experience cognitive decline but generally maintain their independence. They may forget the names of people they see frequently, need a GPS while driving, or make occasional mistakes managing their finances, but they are still able to function independently. By the time dementia develops, some degree of that independence has been lost.

Going back to the pathology, amyloid is the underlying driver, and today we can detect amyloid through blood testing. There are several different blood-based assays available. One of the tests I commonly use in my clinic is plasma P-tau217. It's a simple blood test, much like the laboratory tests we're already accustomed to ordering for hemoglobin A1C or cholesterol.

A positive P-tau217 result does not mean someone has dementia or even memory impairment. However, if a patient presents with memory concerns, and I've ruled out other reversible causes, such as vitamin B12 deficiency, other vitamin deficiencies, or thyroid disease, a positive P-tau217 test allows me to say with a fairly high degree of clinical confidence whether the likelihood of underlying Alzheimer's disease is high or low.

Increasingly, patients are asking whether they can have this testing performed before symptoms develop. At the moment, there are important limitations. Currently, P-tau217 testing is approved for patients who have objective cognitive impairment. In other words, they report memory concerns, and those concerns are confirmed through formal cognitive testing. After reversible causes have been excluded, the blood test can then be used to help support the diagnosis.

It's not approved for everyone. In the United States, the FDA has approved its use in individuals aged 50 years or older who have objective cognitive impairment after other causes of cognitive decline have been ruled out.

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