32 - Instant insights: Blood-based biomarkers for Alzheimer’s Disease (8 min) - Healthier World with Quest Diagnostics

Summary4 min read

Healthier World with Quest Diagnostics
Episode 32 – Instant Insights: Blood-Based Biomarkers for Alzheimer’s Disease
Date: March 2, 2026
Host: Dr. Mason Latsko (Quest Diagnostics)
Duration: 8 minutes

Episode Overview

This Instant Insights episode, hosted by Dr. Mason Latsko, delves into the emerging role of blood-based biomarkers in the diagnosis and management of Alzheimer’s disease. The episode covers the limitations of traditional diagnostic methods, recent advances in blood-based testing, the specific biomarkers involved, and the practical impact on clinical decision-making. Dr. Latsko emphasizes how these innovations may help clinicians achieve earlier and more precise diagnoses, while also differentiating Alzheimer’s from other potential causes of cognitive decline.

Key Discussion Points & Insights

The Challenge of Diagnosing Alzheimer’s Disease

Prevalence:
- Over 55 million people globally, with 7 million older adults in the US living with Alzheimer’s.
- One of the most common and costly neurodegenerative diseases.
Diagnostic Delay:
- Alzheimer’s often diagnosed after symptom onset due to reliance on expensive imaging or invasive tests.
- “Despite how prevalent Alzheimer's disease is, it's often diagnosed late, after symptoms have already begun to interfere with daily life.” (Dr. Latsko, 01:02)

Shift to Blood-Based Biomarkers

Historical Barriers:
- Diagnosis previously relied on brain imaging (PET) or lumbar puncture, not practical for broad early screening.
Evolving Paradigm:
- New blood-based biomarkers now guideline-supported, offering earlier, accessible, less invasive assessment.
- “We're entering into a new era of dementia care, one where blood-based biomarkers are guideline-supported to help clinicians gain biological insights into what's happening in the brain earlier and in a way that's potentially more accessible than ever before.” (Dr. Latsko, 01:25)

Understanding Alzheimer’s Pathology

Key Features:
- Alzheimer’s is characterized by amyloid beta plaques (outside neurons) and tau tangles (inside neurons).
- Amyloid plaques disrupt neuron communication; tau tangles impair internal cell transport, leading to cell death and cognitive decline.
Clinical Overlap:
- Many dementias (vascular, Lewy body, frontotemporal, some reversible causes) share symptoms; biomarkers help clarify etiology.

The Core Biomarkers Discussed

1. Amyloid Beta 42/40 Ratio

Plaque Formation Indicator:
- Amyloid beta 42 builds up in Alzheimer’s, reducing its level in blood relative to beta 40, yielding a low 42/40 ratio.
- “A low plasma Abeta 42/40 ratio has been shown to be correlated with amyloid PET positivity and reflects the process of amyloid plaque deposition.” (Dr. Latsko, 03:14)
Clinical Relevance:
- Offers a non-imaging, non-invasive surrogate of amyloid pathology.
- Particularly useful for patients with mild cognitive impairment.

2. Phosphorylated Tau (P-Tau 217)

Specificity for Alzheimer’s:
- Elevated plasma P-Tau 217 correlates strongly with tau and amyloid PET positivity, indicating Alzheimer’s pathology.
- “Tau pathology is closely linked to neuronal injury and disease progression in Alzheimer's disease.” (Dr. Latsko, 04:14)
Added Value:
- Provides an additional layer of specificity beyond amyloid biomarkers.

3. Combined Testing Approach

Diagnostic Confidence:
- Simultaneous testing improves accuracy in detecting both amyloid and tau pathology.
- “Combining tests such as the Amyloid Beta 42/40 and P Tau 217 can improve diagnostic confidence in symptomatic patients.” (Dr. Latsko, 05:06)

The AD Detect Panel (Quest Diagnostics)

Panel Features:
- Measures both Abeta 42/40 ratio and P-Tau 217.
- Uses a model to generate a likelihood score of PET positivity.
- “...over 90% sensitivity and specificity and a 15% indeterminate rate, which is within acceptable parameters...” (Dr. Latsko, 05:38)
Interpretation:
- High likelihood scores support consideration of Alzheimer's disease and guide next steps; indeterminate results require clinical context.

Differentiating Alzheimer’s from Other Causes

Non-Alzheimer’s Causes:
- Not all cognitive decline is due to Alzheimer's.
- Modifiable secondary causes include diabetes, thyroid disease, kidney disease, fatty liver, sleep disturbances, nutritional deficiencies.
Role of Biomarkers:
- Help distinguish neurodegenerative from reversible/metabolic causes.
- “Blood-based biomarkers serve to indicate whether or not these comorbidities are leading to cognitive impairment or whether symptoms are arising due to amyloid and plaque pathology.” (Dr. Latsko, 06:32)

Practical Applications in Clinical Practice

Advantages:
- Supports differentiation between Alzheimer’s and other dementias.
- Enables earlier intervention and prognosis discussions.
- Guides eligibility for disease modifying therapies or trials.
- Intended for adults over 55 with cognitive symptoms suggestive of mild cognitive impairment.
Role of Clinical Judgement:
- “Blood-based biomarkers are not replacing clinical judgment, but they are enhancing it.” (Dr. Latsko, 07:10)

Notable Quotes & Memorable Moments

On Changing Diagnostic Paradigms:
- “We're entering into a new era of dementia care...” (01:25)
On the Power of Combining Markers:
- “Combining tests such as the Amyloid Beta 42/40 and P Tau 217 can improve diagnostic confidence...” (05:06)
On Clinical Utility:
- “These tests can help support a confident diagnosis decision and help guide next steps.” (07:21)
On the Excitement of the Field:
- “This is a very exciting time for Alzheimer's disease identification.” (07:01)

Key Segment Timestamps

Introduction and Scope of Alzheimer’s Disease: 00:00 – 01:20
Transition to Blood-Based Biomarkers: 01:20 – 02:50
Description of Pathology and Biomarkers: 02:50 – 05:00
Details on AD Detect Panel and Accuracy: 05:00 – 06:00
Non-Alzheimer’s and Modifiable Causes: 06:00 – 06:45
Clinical Implications and Conclusion: 06:45 – 07:50

Summary

Dr. Mason Latsko uses this concise, insightful episode to showcase how blood-based biomarkers (Amyloid Beta 42/40 and P-Tau 217) are transforming Alzheimer’s disease evaluation. The AD Detect panel’s high sensitivity and specificity empower clinicians to identify pathology earlier and more practically than ever before, aiding differentiation from other cognitive disorders and guiding appropriate patient management. As Dr. Latsko concludes, these advances are not a replacement for clinical judgment but a significant enhancement in moving Alzheimer’s diagnosis—and care—into a more hopeful, proactive era.

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[00:00]
A
Foreign welcome to Healthier World with Quest Diagnostics. Our goal is to prompt action from Insight as we keep you up to date on current clinical and diagnostic topics in cardiovascular, metabolic, endocrine and wellness medicine. Welcome to a special episode series called Instant Insights, a podcast episode designed to give you quick and highly impactful clinical pearls in just a few minutes. Dr. I'm Dr. Mason Latsko, and today we'll be discussing blood based biomarkers for Alzheimer's disease. Alzheimer's disease and related dementias are one of the most pressing health challenges that we face today. Globally, around 55 million people are living with dementia, and in the US alone, more than 7 million older adults are currently living with Alzheimer's disease, making it one of the most common and costly neurodegenerative conditions. And yet, despite how prevalent Alzheimer's disease is, it's often diagnosed late, after symptoms have already begun to interfere with daily life. And in part, this is due to the idea that for decades, confirming Alzheimer's disease pathology required expensive imaging or invasive procedures. But over the last several years, that has begun to change. We're entering into a new era of dementia care, one where blood based biomarkers are guidelines supported to help clinicians gain biological insights into what's happening in the brain earlier and in a way that's potentially more accessible than ever before. Alzheimer's disease shares clinical features with many other conditions, including vascular dementia, Lewy body disease, frontotemporal degeneration, and even reversible causes of cognitive impairment. And historically, clinicians relied heavily on clinical assessment to make these types of distinctions. And while helpful, clinical assessment doesn't always tell us whether Alzheimer's disease pathology is actually present. Specifically here we're talking about amyloid beta plaques and tau tangles, and these are hallmark features of Alzheimer's disease. Amyloid beta protein builds up between the neurons and this disrupts communication from neuron to neuron, while tangles is the accumulation of tau protein that accumulates inside the neuron, impairing cell transport and ultimately leading to neuronal death. Together, plaques and tangles drive neurodegeneration and cognitive decline. Now, biomarkers that identify plaques and tangles provide biological evidence of disease and help clinicians move beyond just looking at symptoms alone. The core biomarkers that we'll be talking about here include beta amyloid 4240 ratio, which reflects amyloid plaque deposition, and phosphorylated TAU, or P Tau217, which is closely associated with Alzheimer's specific tau pathology. Biomarkers provide biological evidence of the disease, helping clinicians move beyond symptoms toward a more precise understanding of what's happening in the brain of these patients. Let's first talk about plaque formation. This can be identified by looking at a beta or amyloid beta. Now, one of the most established biomarkers in Alzheimer's disease is beta amyloid 4240 ratio. In Alzheimer's disease, amyloid beta 42, or Abeta 42, accumulates in plaques within the brain, and as a result of this accumulation, levels of Abeta 42 decrease in the circulating blood, especially relative to Abeta 40, resulting in a low ratio. A low plasma Abeta 4240 ratio has been shown to be correlated with amyloid PET positivity and reflects the process of amyloid plaque deposition, meaning that it can serve as a surrogate for amyloid plaque pathology without the requirement of imaging. And this makes it extremely valuable in patients with mild cognitive impairment where determining whether Alzheimer's disease pathology is present can significantly influence next steps. While amyloid biomarkers tell us about plaque deposition, phosphorylated tau biomarkers such as P Tau217 add another critical layer of specificity. Tau pathology is closely linked to neuronal injury and disease progression in Alzheimer's disease, and elevated Plasma P Tau217 levels have been shown to be strongly correlated with both tau and amyloid PET positivity and Alzheimer's pathology. When amyloid and tau biomarkers are assessed together, clinicians gain a more complete picture, helping to identify whether both hallmark features of Alzheimer's disease are present in the brain. And this is why combining tests such as the Amyloid Beta 4240 and P Tau 217 can improve diagnostic confidence in symptomatic patients. At Quest Diagnostics, we offer a suite of testing for Alzheimer's disease risk called AD detect testing, and within that suite of AD detect testing is a panel For AD detect Abeta 4240 ratio and PTAU217, and this panel combines these results into a model that also generates a likelihood score for PET positivity with over 90% sensitivity and specificity and a 15% indeterminate rate, which is within acceptable parameters and indicates that PET positivity cannot be predicted in approximately 15% of people, and results for those patients should be interpreted based on individual biomarkers within the full clinical picture, and this high degree of accuracy may give providers greater confidence to move patients with a high likelihood score for Alzheimer's disease onto a path for treatment. Importantly, not all cognitive decline is due to degenerative disease, and there are several secondary causes of dementia that are key to mention since they are modifiable and partly reversible. And these disease states include metabolic and endocrine disorders such as poorly controlled diabetes, thyroid disease, chronic kidney disease, fatty liver disease, sleep disturbances and even nutritional deficiencies. And these comorbid conditions can really drive symptomatology of Alzheimer's disease. So blood based biomarkers serve to indicate whether or not these comorbidities are leading to cognitive impairment or whether symptoms are arising due to amyloid and plaque pathology. In clinical practice, blood based biomarkers can help to differentiate Alzheimer's disease from non Alzheimer's disease dementias, support early intervention and more informed discussion around prognosis and care planning, and help determine eligibility for disease modifying therapies or clinical trials. Blood based Alzheimer's disease biomarkers are intended for adults older than 55 with cognitive symptoms consistent with mild cognitive impairment. This is a very exciting time for Alzheimer's disease identification. Blood based biomarkers are not replacing clinical judgment, but they are enhancing it. AD detect represents a shift toward earlier and less invasive assessments of Alzheimer's disease pathology and when used in the appropriate clinical context, these tests can help support a confident diagnosis decision and help guide next steps. As our understanding of Alzheimer's disease continues to evolve, so too does our ability to detect and potentially intervene earlier in the disease course. That's a wrap on this episode of Healthier World with Quest Diagnostics. Please follow us on your favorite podcast app and be sure to check out Quest Diagnostics Clinical Education center for more resources, including educational webinars and research publications. Thank you for joining us today as we work to create a healthier world one life at a time.