Amyloid and Tau Are Not Enough. Why Targeting Synaptic Loss May Be the Future of Alzheimer’s Diagnosis

For decades, Alzheimer’s research has focused heavily on amyloid plaques and tau tangles. These hallmark proteins are frequently found in the brains of patients with Alzheimer’s. But mounting evidence now shows that amyloid and tau alone don’t reliably predict cognitive decline, and targeting them doesn’t always improve symptoms.

So, what if the real key to Alzheimer’s lies elsewhere?

The Problem With Amyloid and Tau-Based Testing

Blood and cerebrospinal fluid (CSF) tests typically measure levels of beta-amyloid or phosphorylated tau. While these biomarkers are associated with Alzheimer’s, they can also appear in:

• Older adults with no cognitive symptoms
• Patients with other forms of dementia
• Individuals experiencing natural brain aging

In fact, studies have shown that clearing amyloid plaques from the brain does not consistently lead to improved cognition. One of the most striking findings came from The Lancet Neurology, where patients who underwent plaque-clearing treatments continued to experience cognitive decline.

Synaptic Loss: A Stronger Predictor

Emerging research highlights synaptic density and function as more directly correlated with cognitive ability. A 2006 study by Scheff et al. found that hippocampal synaptic loss aligned more closely with memory decline than amyloid or tau levels.

Synapses are the communication points between neurons. As these connections break down, the brain’s ability to process, store, and retrieve information declines, regardless of how much amyloid is present.

How DISCERN™ Uses This Insight

The DISCERN™ test focuses on morphometric imaging of skin cells to measure markers of neuronal and synaptic dysfunction, rather than indirect risk indicators. It is also validated against autopsy-confirmed Alzheimer’s and non-Alzheimer’s cases, ensuring far greater specificity.

This approach makes DISCERN™ one of the few tools capable of diagnosing Alzheimer’s with over 95% sensitivity and specificity, even in complex or early-stage presentations.

Final Thoughts

Amyloid and tau can indicate brain changes, but they don't offer definitive answers. Measuring the functional damage to neurons and synapses may provide a more accurate path forward.

As diagnostic science evolves, tools like DISCERN™ are helping us shift from assumption to certainty  and from risk to real answers.