My Amyloid Beta 42/40 Ratio Is Low. Do I Have Alzheimer’s?

One line that now appears on many Alzheimer’s blood test reports is the amyloid beta 42/40 ratio, often written Aβ42/40. It may be reported on its own, inside a combined score such as PrecivityAD2, or on a research panel. When it is flagged low, the search results tend to be either technical papers or pages that jump straight to dementia.

This guide explains what the number measures, how far it can be trusted, and what usually comes next. For an overview of the other blood markers (p-tau217, GFAP and NfL), see blood tests for Alzheimer’s risk.

The Short Answer

A low Aβ42/40 ratio in blood means that amyloid plaques, the earliest recognized brain change of Alzheimer’s disease, are more likely to be present.^1,2 It is a statement about biology, not a diagnosis of dementia, and it does not tell you whether or when symptoms will appear.

It is also one of the less precise blood biomarkers. The plasma ratio is only about 10 to 15 percent lower when plaques are present, against roughly 50 percent in spinal fluid, so small errors in the laboratory or in sample handling can move a result across the cutoff.^2,3 In a 2024 head-to-head study of commercial tests, the plasma ratio classified amyloid status clearly less accurately than p-tau217.⁴ A low ratio is a reason to look further, usually with a p-tau217 test, and with amyloid PET or spinal fluid testing when a major decision depends on the answer.

What does the amyloid beta 42/40 ratio measure?

Amyloid beta (Aβ) is a small protein fragment that the brain produces continuously, in several lengths. Blood tests measure two of them: Aβ42 and the slightly shorter Aβ40. Aggregation-prone Aβ peptides are the building blocks of the plaques that define Alzheimer’s disease.²

As plaques form, the ratio of Aβ42 to Aβ40 falls in both spinal fluid and blood.¹ In the Swedish BioFINDER cohort, people with brain amyloid had lower plasma Aβ42 and a lower Aβ42/40 ratio on every assay tested, while Aβ40 did not differ between the groups.⁵ The accepted interpretation is that Aβ42, the form that aggregates, is increasingly held in plaques in the brain, so relatively less of it circulates. That is why a low ratio points toward more amyloid in the brain, which many people find counterintuitive.

Blood is an indirect window. Much of the Aβ in plasma is made outside the brain, which is one reason plasma and spinal fluid values agree only moderately.¹

Why is the ratio used instead of Aβ42 alone?

Dividing Aβ42 by Aβ40 cancels out influences that push both peptides up or down together. In two Swedish cohorts of 748 and 421 people, kidney function (measured by creatinine), body mass index, hypertension, diabetes and some blood pressure and lipid-lowering medicines were associated with plasma Aβ42 and Aβ40 individually, but not with their ratio.⁶

Creatinine and body mass were associated, to a lesser extent, with p-tau.⁶ That is why kidney function is one of the first things to check after a positive p-tau217 blood test, and less of a concern for the amyloid ratio.

What counts as a low Aβ42/40 ratio?

There is no universal normal value. Each platform measures the peptides differently, so each has its own scale and its own cutoff. In the BioFINDER comparison, the median ratio in amyloid-negative people was 0.068 on the Roche Elecsys immunoassay and 0.322 on the Araclon mass spectrometry method, run on the same samples.⁵

Two published cutoffs show the spread:

• Washington University mass spectrometry assay (the method behind a test now used in U.S. clinical care⁵): a ratio below 0.1218 was classed as positive in a 2019 study of 158 mostly cognitively normal people.⁷
• Quest Diagnostics mass spectrometry assay: 0.160 was the best single cutpoint against amyloid PET, and the authors proposed treating 0.150 to 0.170 as an indeterminate zone.⁸

A value that counts as low on one platform can be normal on another. Read your number only against the cutoff printed on your own report, and do not compare results from different laboratories. Combined tests such as PrecivityAD2 may print the ratio but base the final call on an overall score, described below.

How accurate is a low Aβ42/40 ratio compared with amyloid PET?

Moderately accurate, and highly dependent on the assay. Accuracy is often reported as AUC (area under the curve), on a scale where 0.5 is a coin flip and 1.0 is perfect.

• 2021, eight assays on the same samples: in 286 BioFINDER participants without dementia, AUCs for detecting abnormal amyloid ranged from 0.64 to 0.87. The best mass spectrometry methods outperformed most immunoassays.⁵
• 2024, leading commercial tests: in 392 participants of the Alzheimer’s Disease Neuroimaging Initiative, Aβ42/40 ratios from four manufacturers had AUCs of 0.73 to 0.79 against amyloid PET. p-tau217 tests on the same samples reached 0.88 to 0.93.⁴
• Adding age and APOE: in the 2019 Washington University study, the ratio alone had an AUC of 0.88 against amyloid PET, rising to 0.94 when age and APOE ε4 status were added.⁷

In 2021, the best ratio assay performed about as well as the p-tau217 assay then available (AUC 0.86 against 0.79, not a significant difference).⁵ With newer p-tau217 tests, the 2024 authors concluded that plasma Aβ42/40 had relatively low accuracy for amyloid status.⁴

Why is the plasma Aβ42/40 ratio less reliable than p-tau217?

The core problem is a small signal. In spinal fluid, the Aβ42/40 ratio is about 50 percent lower in people with amyloid pathology. In plasma, the difference is only 10 to 15 percent, and the 2024 Alzheimer’s Association diagnostic criteria attribute the weaker robustness of plasma ratio assays, compared with spinal fluid tests and plasma p-tau217, to this narrow range.² In the 2024 commercial comparison, median plasma ratios were 10 to 13 percent lower in amyloid-positive people.⁴

When the gap between normal and abnormal is that narrow, ordinary laboratory variation matters. Simulations based on the Roche Elecsys assay showed that small measurement or pre-analytical errors caused misclassifications.³ The 2025 Alzheimer’s Association guideline makes the same point: markers with small differences between positive and negative people, such as Aβ42/40, are more susceptible to assay imprecision in routine use.⁹

What can make an Aβ42/40 result falsely low or falsely high?

• Sample handling. Aβ42 and Aβ40 are unstable in whole blood, and a 2023 expert review advises centrifuging samples early, ideally within 1 hour.¹ In the Standardization of Alzheimer’s Blood Biomarkers study, a 24-hour delay at room temperature lowered both peptides, Aβ42 somewhat more than Aβ40, and using the ratio did not cancel the effect for most of the six assays tested.¹⁰
• Collection tube. The type of blood tube changed the measured values of every marker tested.¹⁰
• The assay itself. Accuracy differed widely across the eight methods run on identical samples.⁵

Errors can run in either direction, producing a false positive or a false negative.³ Kidney function and body weight, which can shift p-tau217, were not associated with the ratio.⁶

What are combined tests like PrecivityAD2 and Lumipulse?

Because the ratio is weaker on its own, the leading clinical tests pair amyloid with p-tau217.

• PrecivityAD2 (C2N Diagnostics) measures plasma Aβ42/40 and %p-tau217 (phosphorylated tau217 relative to the non-phosphorylated form) by mass spectrometry and combines them into an Amyloid Probability Score 2 (APS2). In a company-led validation study of 583 people with suspected Alzheimer’s disease, the APS2 had an AUC of 0.94 and agreed with amyloid PET 88 percent of the time. %p-tau217 alone also reached an AUC of 0.94.¹¹ In August 2026, the FDA cleared PrecivityAD2 for adults 40 and older with signs or symptoms of cognitive impairment.¹²
• Lumipulse G (Fujirebio) reports a ratio of p-tau217 to Aβ42 rather than Aβ42/40. On May 16, 2025, it became the first FDA-cleared blood test used in diagnosing Alzheimer’s disease, for adults 55 and older with signs and symptoms. In 499 samples from cognitively impaired adults, 91.7 percent of positive results and 97.3 percent of negative results matched PET or spinal fluid, and fewer than 20 percent of results were indeterminate.¹³

If your report shows a combined score, interpret the score rather than the ratio line on its own. For how the cleared tests differ, see the FDA-cleared Alzheimer’s blood tests compared.

Does a low Aβ42/40 ratio mean something different with or without symptoms?

Yes. Under the Alzheimer’s Association’s 2024 revised criteria, Alzheimer’s disease is defined biologically, and an abnormal result on an accurate amyloid biomarker is enough to establish the diagnosis. A plasma test qualifies only if it reaches at least 90 percent accuracy for amyloid PET in its intended population, and accuracy varies substantially among plasma Aβ42/40 assays.²

With memory or thinking symptoms, a low ratio raises the probability that Alzheimer’s pathology is contributing. The 2025 Alzheimer’s Association guideline, written for specialist care of people with measurable cognitive impairment, says a blood test can be used for triage if it has at least 90 percent sensitivity (it catches 9 in 10 people with amyloid) and 75 percent specificity (it correctly clears 3 in 4 without), and can replace PET or spinal fluid testing only if both reach 90 percent. It warns that many commercial tests do not meet these thresholds, and that blood tests do not replace a full clinical evaluation.⁹

Without symptoms, a confirmed abnormal amyloid biomarker places someone in what the criteria call clinical stage 1: asymptomatic, with biomarker evidence only.² It is not dementia. In an Australian cohort of 599 cognitively normal older adults followed for 8 years, 17.7 percent of those with amyloid on PET progressed to mild cognitive impairment or dementia, against 8.1 percent of those without.¹⁴ A low plasma ratio can also come before a positive scan: in the 2019 Washington University study, people with a negative amyloid PET but a positive plasma ratio had a 15-fold higher risk of later converting to a positive scan.⁷

The 2024 criteria recommend against diagnostic testing of cognitively unimpaired people for clinical purposes outside research,² and the 2025 guideline does not extend to them.⁹ A result you already hold is not meaningless, but the evidence for acting on it is thinner.

What do different combinations of Aβ42/40 and p-tau217 results suggest?

What should you do after a low Aβ42/40 result?

• Identify the test and its cutoff. Find the assay name, the laboratory and the reference cutoff on the full report. Ask how quickly the sample was processed.
• Check whether p-tau217 was measured. If not, a p-tau217 test or a combined test is the usual next step, because it classifies amyloid status more accurately.⁴
• Confirm when a decision depends on it. If the result could lead to treatment, a clinical trial or a major life decision, amyloid PET or spinal fluid testing remains the reference standard.⁹
• Measure cognition properly. A formal cognitive baseline tells you which situation you are in, symptomatic or not. A brain health assessment covers this and the rest of the workup.
• Review vascular and metabolic risk. Blood pressure, blood sugar, lipids, sleep and hearing belong in a prevention plan whatever the amyloid result.
• Know your APOE status. APOE ε4 is closely tied to amyloid: in BioFINDER, 65 percent of amyloid-positive participants carried it, against 21 percent of amyloid-negative ones, and adding it improves the ratio’s accuracy.^5,7
• Set a follow-up plan. If you repeat the test, use the same assay at the same laboratory, because values are not comparable across platforms.⁵

Common Questions

Does a low amyloid beta 42/40 ratio mean I have Alzheimer’s disease?

Not on its own. It raises the probability that amyloid plaques are present. With memory symptoms, it supports Alzheimer’s disease as a possible cause but needs confirmation. Without symptoms, even a confirmed result describes an early biological stage, not dementia.

What is a normal Aβ42/40 ratio?

There is no universal normal value. Cutoffs differ by platform: a published research cutoff for one mass spectrometry assay is 0.1218,⁷ while another laboratory’s assay uses 0.160.⁸ Use the cutoff printed on your own report.

Is the Aβ42/40 ratio as accurate as p-tau217?

No. In a 2024 head-to-head study of commercial tests, plasma Aβ42/40 ratios identified amyloid on PET less accurately than p-tau217 tests run on the same samples. Combined tests use both, with p-tau217 carrying most of the accuracy.

Can sample handling cause a falsely low ratio?

Yes. Aβ42 and Aβ40 degrade in whole blood if the sample is not processed promptly, and long delays at room temperature lower Aβ42 somewhat more than Aβ40. Because the difference between normal and abnormal is small, handling errors can change the classification.

Does kidney function affect the Aβ42/40 ratio?

Less than it affects other markers. In large Swedish cohorts, creatinine and body mass index were linked to Aβ42 and Aβ40 individually but not to their ratio. Kidney function matters more when interpreting p-tau217.

Should I get an Aβ42/40 test if I have no symptoms?

Current Alzheimer’s Association criteria recommend against diagnostic testing of cognitively unimpaired people for clinical purposes outside research. If you already have a result, the useful next step is a plan built around it, not a new test chosen at random.

The Bottom Line

A low amyloid beta 42/40 ratio is a signal worth taking seriously and a weak one to act on alone. It suggests amyloid may be building up, but the plasma ratio has a narrow range and is sensitive to how the sample was handled.

The productive response is to find out which test you had, add or confirm with a more accurate marker when the answer matters, measure cognition, and work on the risk factors you can change. A structured brain health assessment brings those steps together.

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Dr. Nadir Bilici, MD, DipIBLM, is a board-certified neurologist (ABPN) and Diplomate of the International Board of Lifestyle Medicine specializing in preventive neurology, Alzheimer’s prevention, and cognitive risk assessment. He sees patients by telehealth in the states where he is licensed, with in-person appointments available on a select basis.

References

1. Hansson O, Blennow K, Zetterberg H, Dage J. Blood biomarkers for Alzheimer's disease in clinical practice and trials. Nat Aging. 2023;3(5):506-519. doi:10.1038/s43587-023-00403-3
2. Jack CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024;20(8):5143-5169. doi:10.1002/alz.13859
3. Rabe C, Bittner T, Jethwa A, et al. Clinical performance and robustness evaluation of plasma amyloid-β42/40 prescreening. Alzheimers Dement. 2023;19(4):1393-1402. doi:10.1002/alz.12801
4. Schindler SE, Petersen KK, Saef B, et al. Head-to-head comparison of leading blood tests for Alzheimer's disease pathology. Alzheimers Dement. 2024;20(11):8074-8096. doi:10.1002/alz.14315
5. Janelidze S, Teunissen CE, Zetterberg H, et al. Head-to-head comparison of 8 plasma amyloid-β 42/40 assays in Alzheimer disease. JAMA Neurol. 2021;78(11):1375-1382. doi:10.1001/jamaneurol.2021.3180
6. Pichet Binette A, Janelidze S, Cullen N, et al. Confounding factors of Alzheimer's disease plasma biomarkers and their impact on clinical performance. Alzheimers Dement. 2023;19(4):1403-1414. doi:10.1002/alz.12787
7. Schindler SE, Bollinger JG, Ovod V, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93(17):e1647-e1659. doi:10.1212/WNL.0000000000008081
8. Weber DM, Taylor SW, Lagier RJ, et al. Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer's disease assessment. Front Neurol. 2024;15:1364658. doi:10.3389/fneur.2024.1364658
9. Palmqvist S, Whitson HE, Allen LA, et al. Alzheimer's Association clinical practice guideline on the use of blood-based biomarkers in the diagnostic workup of suspected Alzheimer's disease within specialized care settings. Alzheimers Dement. 2025;21(7):e70535. doi:10.1002/alz.70535
10. Verberk IMW, Misdorp EO, Koelewijn J, et al. Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease-related blood-based biomarkers: results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group. Alzheimers Dement. 2022;18(8):1484-1497. doi:10.1002/alz.12510
11. Meyer MR, Kirmess KM, Eastwood S, et al. Clinical validation of the PrecivityAD2 blood test: a mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid. Alzheimers Dement. 2024;20(5):3179-3192. doi:10.1002/alz.13764
12. Alzheimer's Association. Alzheimer's Association statement on FDA clearance of PrecivityAD2 blood test for Alzheimer's diagnosis in adults as young as 40. Press release. Published August 20, 2026. alz.org/news/2026/fda-clearance-precivityad2-blood-test-alzheimers
13. U.S. Food and Drug Administration. FDA clears first blood test used in diagnosing Alzheimer's disease. Press release. Published May 16, 2025. fda.gov/news-events/press-announcements/fda-clears-first-blood-test-used-diagnosing-alzheimers-disease
14. Dang C, Harrington KD, Lim YY, et al. Relationship between amyloid-β positivity and progression to mild cognitive impairment or dementia over 8 years in cognitively normal older adults. J Alzheimers Dis. 2018;65(4):1313-1325. doi:10.3233/JAD-180507

Written and medically reviewed by Nadir Bilici, MD, DipIBLM. Published October 2026 · Medically reviewed on October 5, 2026. See our editorial policy.