Amyloid Beta 42/40 Ratio

What is Amyloid Beta 42/40 Ratio?

The amyloid beta 42/40 ratio divides two protein fragments measured in blood plasma or spinal fluid.

The ratio is one number made from two. A lab measures amyloid beta 42 (Aβ42) and amyloid beta 40 (Aβ40), two fragments of the same larger protein, and divides the first by the second. LOINC, the coding system labs use to name results, defines it exactly that way: the concentration of Aβ42 divided by Aβ40. The result has no units. It's a decimal, and how it reads depends on the lab's method. Why divide at all? Because a ratio cancels some of what moves both fragments together. A 2023 study of plasma and spinal fluid assays noted that the ratio could help overcome the effect of kidney function on the individual peptides. Sample handling is another example, though a 2021 handling study found the ratio offset delays only for some assays and some conditions. The catch is how small the signal is. In Alzheimer's disease, the ratio in spinal fluid (CSF) falls by roughly 50 percent. In plasma, the difference is about 14 to 20 percent, the authors of the same 2023 study of 134 people observed. A shift that small sits close to the noise of the measurement, so precision matters more here than for most blood markers. In that study, two plasma immunoassays correlated weakly with each other (Spearman ρ=0.47), while the same two assays agreed closely in CSF (ρ=0.93). A 2024 evaluation of a mass spectrometry method reported an area under the curve (AUC) of 0.84 against amyloid PET, where 1.0 is perfect separation and 0.5 is a coin flip. That's useful for a specialist weighing options. It's not a number that settles anything alone. Plasma, CSF, and amyloid PET are three different measurements. PET images amyloid in the brain. A CSF test measures amyloid and tau in fluid collected by lumbar puncture, which the Alzheimer's Association describes as minimally invasive. A plasma test uses a blood draw. The newer blood tests are evaluated against PET or CSF, and the FDA's own language for the first cleared test says the result correlates with amyloid plaques "reducing the need for a PET scan", not that it replaces clinical judgment. Here's where things stand as of October 2026. The Alzheimer's Association published a clinical practice guideline on blood-based biomarkers in July 2025. It covers adults with objective cognitive impairment who are being evaluated by memory-care specialists. It sets two performance bars: at least 90 percent sensitivity and 75 percent specificity for a triage role, and at least 90 percent for both for a confirmatory role. It's written about tests, not brands. In the evidence tables, none of the eleven Aβ42/40 assays listed reached the confirmatory bar, and one immunoassay reached the triage bar. The assays that reached the confirmatory bar in those tables used p-tau217, a different protein. That distinction runs through the FDA clearances too. Four blood tests have been cleared, per the Alzheimer's Association and Rutgers Brain Health Institute. Fujirebio's Lumipulse (May 2025) uses the ratio of pTau217 to Aβ1-42, which is not Aβ42/40. Roche's Elecsys pTau181 (October 2025) and Elecsys pTau217 (August 24, 2026) each measure a single tau analyte. C2N Diagnostics' PrecivityAD2 (August 20, 2026) is the only cleared test that includes Aβ42/40: it measures the ratio by mass spectrometry, combines it with a p-tau217 ratio, and reports one score. None of the four reports Aβ42/40 on its own. The plasma Aβ42/40 tests from Quest and Labcorp state they're lab-developed and not cleared or approved by the FDA. The FDA's and manufacturers' descriptions share one frame: an aid for adults with signs or symptoms of cognitive impairment, interpreted with other clinical information. If this ratio shows up in your records, keep the lab's method and the cutoff it printed next to the number. The same ratio from two different methods isn't comparable, and that detail is easy to lose once a PDF is filed away. Longetic keeps the report organized and searchable, so those details travel with the number into your next appointment.

Typical reference context

These are decision cutoffs for people already being evaluated for cognitive symptoms, set separately by each lab and method. They aren't ranges of "healthy" values, and the CSF and plasma numbers can't be compared with each other. Quest's brochure also describes an intermediate band of 0.150 to 0.169. Which cutoff applies to a given result is a question for the clinician who ordered it.

What changed recently

The biggest change is regulatory. In May 2025, the FDA cleared the first blood test to aid Alzheimer's diagnosis, Fujirebio's Lumipulse pTau217/β-Amyloid 1-42 plasma ratio. In its press release the FDA reported a positive predictive value of 91.7 percent and a negative predictive value of 97.3 percent, with fewer than 20 percent of 499 patients getting an indeterminate result, and said the test is not intended as a screening or stand-alone diagnostic test. In July 2025 the Alzheimer's Association guideline set the sensitivity and specificity bars described above. Then came three more clearances: Elecsys pTau181 in October 2025, PrecivityAD2 on August 20, 2026, and Elecsys pTau217 on August 24, 2026.

For Aβ42/40 specifically, the story is one of cautious progress. The 2024 mass spectrometry evaluation reached an AUC of 0.84. A 2025 preprint from French memory clinics (423 participants, a preprint, so not yet peer reviewed) found plasma Aβ42/40 at 0.84 versus 0.909 for pTau217 alone, and 0.927 for a pTau217/Aβ42 ratio. Roche's Elecsys pTau217 labeling adds that its safety and effectiveness haven't been established for predicting dementia.

Tests often checked alongside this

In specialist evaluations, the ratio sits next to other measures of the same question. Plasma p-tau217 and p-tau181 are the tau markers behind most cleared blood tests. CSF testing measures amyloid and tau directly in spinal fluid, and amyloid PET images amyloid in the brain. Clinicians also use cognitive testing and a medical history, which the guideline says blood biomarkers complement rather than replace.

What can affect this marker

Sample handling matters here. In a 2021 study from the Standardization of Alzheimer's Blood Biomarkers working group, Aβ42 and Aβ40 dropped when blood sat at room temperature for 24 hours before centrifugation, and refrigeration limited that drop. That study didn't examine fasting, and the Labcorp and Quest pages don't list fasting instructions either. Labcorp asks for an EDTA tube spun within 40 minutes of the draw. Quest asks for K2 EDTA plasma in a polypropylene tube, separated within one hour. For CSF, Mayo notes that polystyrene tubes can give falsely low amyloid values.

The guideline also lists conditions and medicines that can affect biomarker levels, including severe kidney disease and neprilysin inhibitors. Whether any of that applies to a given result is a question for the specialist.

What to ask your doctor

• Which test did the lab run, and does it report the Aβ42/40 ratio alone or combined with p-tau217?
• Was this part of an evaluation for memory or thinking symptoms, and how does it fit with the other findings?
• Which cutoff did the lab use, and does it apply to the method on my report?
• Would this result change the next step compared with a spinal fluid test or an amyloid PET scan?

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