A major breakthrough in Alzheimer’s testing has arrived with the development of highly accurate blood-based biomarkers, offering a simpler, less invasive alternative to spinal taps and costly brain scans. These tests measure proteins linked to the disease, such as tau, amyloid beta (Aβ), and glial fibrillary acidic protein (GFAP), providing a clear window into the brain’s pathology from just a blood draw. For the first time, clinicians can reliably detect and even track Alzheimer’s changes in living patients with speed, accessibility, and affordability, opening the door to earlier diagnosis, better treatment planning, and improved opportunities for patients to participate in new therapies and clinical trials.
Tau217/Aβ42 ratio
This test compares phosphorylated tau-217 (pTau217), a marker of abnormal tau tangles, with amyloid-beta 42 (Aβ42), which declines as plaques form in the brain. The ratio strengthens diagnostic accuracy by showing how tau pathology relates to amyloid burden, and is considered one of the most reliable single measures for distinguishing Alzheimer’s from other dementias.
Phosphorylated tau at threonine 217 (pTau217) rises in Alzheimer’s because abnormal tau accumulates inside neurons. High pTau217 / Aβ42 ratio is strongly suggests Alzheimer’s pathology, since it combines evidence of neurofibrillary tangles (tau) with amyloid plaques (low Aβ42). This ratio is often more accurate than either marker alone in distinguishing AD from normal aging or other dementias.
Interpretation:
- Elevated ratio (positive) → Likely Alzheimer’s disease process.
- Low/normal ratio → Less consistent with AD; cognitive symptoms may stem from another cause.
Aβ42/Aβ40 ratio
This test measures the balance between two forms of amyloid-beta. Aβ42 is prone to clump into plaques, while Aβ40 remains more stable. When the Aβ42/Aβ40 ratio is low, it suggests amyloid plaque accumulation in the brain – one of the earliest hallmarks of Alzheimer’s disease. Aβ42 is the more aggregation-prone peptide; it decreases in blood/CSF as plaques build in the brain. Aβ40 is more stable and serves as a baseline. A low Aβ42/Aβ40 ratio = evidence of amyloid plaque deposition.
Interpretation:
- Low ratio (below assay cutoff) → Suggests amyloid pathology (Alzheimer’s hallmark).
- Normal ratio → Less likely to have amyloid plaques.
Glial Fibrillary Acidic Protein (GFAP)
GFAP is a structural protein in astrocytes, the star-shaped support cells of the brain. Elevated levels in blood reflect astrocytic activation and neuroinflammation, which often occur early in the Alzheimer’s process around amyloid deposits, making GFAP a sensitive marker of brain changes even before severe symptoms develop.
Interpretation:
- Elevated GFAP → Indicates neuroinflammation and astrocytic response, often rising before symptoms are severe. It supports the presence of underlying AD pathology when combined with amyloid/tau results.
- Normal GFAP → Less supportive of active AD-related changes, though it doesn’t rule it out.
Z-score
What it means:
Many labs report a Z-score for these biomarkers, which tells you how far the patient’s value deviates from the mean of a reference (control) population.
- Z = 0 → Average/normal.
- Z > +1 to +2 → Above normal range (elevated, possibly pathological)
- Z < –1 to –2 → Below normal range.
Interpretation:
- A positive Z-score for pTau217 or GFAP → elevated, supports AD pathology.
- A negative Z-score for Aβ42/Aβ40 → decreased ratio, supports amyloid plaque presence.
Putting it All Together
- pTau217/Aβ42 ↑, Aβ42/Aβ40 ↓, GFAP ↑ → Classic Alzheimer’s profile; highly predictive when symptoms are present.
- Normal ratios and GFAP → Alzheimer’s pathology less likely; consider other causes of cognitive impairment.
- Mixed results (e.g., low amyloid but normal tau) → Could represent preclinical stage, early disease, or another neurodegenerative condition.
Bottom line
- Tau217/Aβ42 ratio = strongest indicator of AD vs non-AD dementia.
- Aβ42/Aβ40 ratio = amyloid burden marker.
- GFAP = astrocytic/neuroinflammatory response marker.
- Z-scores = show how abnormal each value is relative to healthy controls.
