By Karen Leggett, DO
For decades, the diagnosis of Alzheimer’s disease and other dementias relied primarily on cognitive testing, brain imaging, and – when necessary – spinal fluid analysis. While these tools remain important, medicine is now entering a new era: the era of blood-based biomarkers for dementia.
These simple blood tests are transforming how we detect, evaluate, and understand cognitive change – often years before symptoms become severe.
Why Early Detection Matters
Many people notice subtle changes long before a diagnosis is made:
• Misplacing items more often
• Trouble recalling recent conversations
• Word-finding difficulty
• Increased mental fatigue
This stage is often called subjective cognitive decline or mild cognitive impairment (MCI). At this point, the brain may already be developing disease-related changes—especially in Alzheimer’s disease—even though daily function remains mostly intact.
Identifying the biology behind these changes early allows us to:
• Clarify the likely cause of symptoms
• Estimate risk of progression
• Guide further testing
• Begin prevention and treatment strategies sooner
What Are Blood Biomarkers?
Blood biomarkers are proteins released into the bloodstream that reflect what is happening in the brain. In dementia, they can signal three major processes:
1. Amyloid accumulation – a hallmark of Alzheimer’s disease
2. Tau pathology – the process that closely tracks nerve cell injury
3. Neurodegeneration – general injury to brain cells, regardless of cause
Together, these markers help us distinguish Alzheimer’s disease from other causes of cognitive decline.
The Two Most Important Alzheimer’s Blood Markers Today
In current clinical studies and practice, two markers stand out.
1. Amyloid Beta 42/40 Ratio (Aβ42/40)
Amyloid beta is a protein that accumulates in the brains of people with Alzheimer’s disease.
• A lower Aβ42/40 ratio suggests amyloid plaques are building up in the brain
• This change often appears years before dementia develops
• It helps identify who is likely developing Alzheimer’s pathology
This marker answers the question: Is Alzheimer-type amyloid biology present?
2. Phosphorylated Tau 217 (p-tau217)
Tau is a protein inside nerve cells that becomes abnormal in Alzheimer’s disease.
• p-tau217 is currently the most specific blood marker for Alzheimer’s disease
• Elevated levels strongly correlate with both amyloid plaques and tau tangles on brain scans
• It helps distinguish Alzheimer’s disease from other dementias
This marker answers the question: Is this cognitive change biologically consistent with Alzheimer’s disease? When both Aβ42/40 is low and p-tau217 is elevated, the likelihood of underlying Alzheimer’s disease is high.
Markers That Suggest Other Types of Dementia
Not all cognitive decline is Alzheimer’s disease.
Other causes include:
• Frontotemporal dementia (FTD)
• Vascular cognitive impairment
• Lewy body dementia
• Parkinson’s disease dementia
• Inflammatory or metabolic brain injury
One important marker here is:
Neurofilament Light Chain (NfL) NfL is a marker of active nerve cell injury.
• Elevated in many neurodegenerative diseases
• Not specific for Alzheimer’s disease
• Helps detect how active and aggressive the process is
How These Tests Are Used in Practice
Blood biomarkers are not used in isolation. They are combined with:
• Detailed history and cognitive testing
• Brain MRI
• Hearing, sleep, mood, and metabolic evaluation
• Review of medications and vascular risk factors
They help answer key clinical questions:
• Is Alzheimer’s biology present?
• Is this more likely vascular, frontotemporal, or mixed?
• How active is the disease process?
• Who should go on to PET scanning or spinal fluid testing?
Why This Matters for Patients 50 and Up
We now know that Alzheimer’s disease begins 10–20 years before dementia.
This opens a new opportunity to:
• Identify risk early
• Modify lifestyle and vascular factors
• Optimize sleep, hearing, mood, and nutrition
• Consider emerging disease-modifying therapies
• Monitor progression more accurately
Brain health is no longer something we address only after memory is lost. It is something we can evaluate, protect, and preserve earlier than ever before.
Final Thoughts
Blood biomarkers are changing the landscape of dementia care. They allow us to move from: “We think this might be Alzheimer’s disease” to “We can now see the biology of what is happening in your brain.” For patients with memory concerns, this represents a profound shift toward earlier clarity, earlier prevention, and more personalized care.
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