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. 2026 Jun 29;18(3):e70387. doi: 10.1002/dad2.70387

Performing multiple biomarker tests delays initiation of amyloid‐targeting treatments

Anna Hofmann 1,2,✉, Madeline Paczynski 1,2, Maria R Ponisio 3, Benjamin Saef 1, Jessica P Roberts 1, William J B Powell 4, Aditi Gupta 4, Inez Oh 4, Mackenzie Hofford 4, Zachary Posey 1, Melissa Aldinger 1, Tammie L S Benzinger 3, John C Morris 1,2, B Joy Snider 1,2, Suzanne E Schindler 1,2,✉
PMCID: PMC13314552  PMID: 42382036

Abstract

INTRODUCTION

With the clinical availability of amyloid‐targeting treatments (ATTs), accurate and timely biomarker‐based diagnosis of Alzheimer's disease (AD) has become increasingly important. Three AD biomarker modalities are commonly available in clinical practice: amyloid positron emission tomography (PET), cerebrospinal fluid (CSF) tests, and blood tests.

METHODS

We investigated the use and agreement of different biomarker modalities in a memory clinic. Further, we calculated the time until ATT initiation for patients who underwent a single test versus multiple biomarker tests.

RESULTS

The blood test agreed with amyloid PET in nine of 11 patients and CSF tests in all 14 patients. The median time from first clinic visit to ATT initiation was 4.7 months in 209 patients who underwent a single test and 8.1 months in 12 patients who underwent multiple tests.

DISCUSSION

Performing multiple biomarker tests delays initiation of ATT and should be restricted to patients with uncertain amyloid status following the first biomarker test.

Keywords: Alzheimer's disease, amyloid‐targeting treatment, blood biomarkers, clinical implementation, door‐to‐needle time

Highlights

  • Alzheimer's blood tests have high agreement with amyloid PET and CSF tests.

  • Continuous values for blood and CSF tests are strongly correlated.

  • Multiple biomarker testing was associated with longer time until treatment.

1. INTRODUCTION

With growing clinical availability of the first‐ever disease‐modifying therapies for early symptomatic Alzheimer's disease (AD), the amyloid‐targeting treatments (ATTs) lecanemab and donanemab, accurate biomarker‐based diagnosis of AD has become increasingly important. 1 , 2 Until recently, amyloid positron emission tomography (PET) scans and cerebrospinal fluid (CSF) tests were used by memory specialists in occasional cognitively impaired patients to determine whether AD pathology was present and could be causing or contributing to cognitive impairment. 3 , 4 Amyloid PET and CSF tests have high but imperfect agreement with one another in the detection of amyloid pathology. 5 , 6 Both modalities have significant drawbacks that limit testing, including invasiveness, burden to patients and providers, and the need for specialized equipment and personnel. In contrast, new blood tests for AD pathology are more acceptable, easily accessible, and highly scalable, making them ideally suited for broad use in clinical diagnosis. 7

Several AD blood tests with accuracy similar to CSF tests in distinguishing amyloid PET status are now available for clinical use. 7 , 8 , 9 , 10 Notably, AD blood tests may not be the optimal biomarker modality for every patient, including those with moderate to severe chronic kidney disease 11 or those taking certain medications. 12 Nevertheless, studies in both primary and secondary care populations have demonstrated that AD blood tests significantly improve diagnostic accuracy for symptomatic AD. 13 By integrating biomarkers with clinical factors, clinicians can reach very high levels of certainty about the likelihood of amyloid pathology in many patients. 14 , 15 Patients with a typical AD dementia syndrome and clearly positive blood biomarker results have a very high likelihood of amyloid pathology. Nevertheless, under certain circumstances (e.g., clinician uncertainty about the accuracy of AD blood tests, insurance reimbursement, and/or institutional policy issues), providers may seek “confirmation” with an amyloid PET scan or CSF test, even if these additional tests do not significantly increase the already very high diagnostic certainty. 16

However, performing an additional biomarker test may not be necessary in patients with a very high likelihood of amyloid pathology and is likely to increase the time until diagnosis and treatment initiation. As pivotal phase 3 clinical trials demonstrated that ATTs slow clinical progression by approximately 6 months over 18 months of treatment 1 , 2 and are likely more effective the earlier they are initiated, 1 the diagnosis of symptomatic AD including biomarker testing is now time‐sensitive for potential treatment candidates. Based on the understanding that “time is brain” for time‐sensitive interventions, the concept of “door‐to‐needle time” was introduced by the American Stroke Association in the 1990s as a key quality metric for thrombolytic treatment. 17 While the relevant timescale in symptomatic AD is not measured in minutes but in months or years, the fundamental concept is that delayed treatment initiation may reduce treatment efficacy.

RESEARCH IN CONTEXT

  1. Systematic review: Traditional databases such as PubMed and Google Scholar were searched for literature on experiences with biomarker tests for AD pathology and ATTs in real‐world memory clinics.

  2. Interpretation: Three different AD biomarker modalities are commonly available in clinical practice to determine eligibility for ATTs: amyloid PET, CSF tests, and blood tests. Some experts recommend following a positive AD blood test with either an amyloid PET or CSF test, even if a highly accurate blood test is used. However, performing multiple biomarker tests may delay initiation of ATTs.

  3. Future directions: The agreement between different AD biomarker modalities under real‐world conditions should be further investigated. The conditions under which a second biomarker test is indicated should be defined.

The Washington University Memory Diagnostic Center (MDC) in St. Louis, Missouri, annually sees approximately 4000 unique patients with memory and thinking concerns. Approximately 6% of patients presenting at MDC ultimately receive ATTs. 18 For diagnostic purposes as well as to determine ATT eligibility, AD biomarker testing via amyloid PET, CSF testing, or blood tests 19 is regularly performed at MDC, with some patients undergoing more than one biomarker test. This study first examined the agreement between AD biomarker modalities in this real‐world memory clinic. Further, the study evaluated the time between the first biomarker test and initiation of lecanemab (door‐to‐needle time for ATTs) for individuals who underwent a single test versus multiple biomarker tests.

2. METHODS

2.1. Clinical Cohort

The MDC is the faculty outpatient clinical practice affiliated with Washington University and receives referrals from a large catchment area primarily located in Missouri and Illinois. 20 Patients who received at least one AD biomarker test as part of their diagnostic workup and/or to determine ATT eligibility at the MDC between July 2021 and March 2025 were included. The subcohort that subsequently initiated treatment with lecanemab was identified through manual chart review of infusion clinic records. Further clinical data were retrospectively collected from electronic health records (EHRs).

2.2. Data extraction from EHRs

Clinical variables were automatically extracted from EHRs: demographics (age, sex, race, ethnicity, body mass index [BMI]); medical comorbidities based on diagnostic codes (chronic kidney disease); laboratory values (creatinine, glomerular filtration rate [GFR]); and clinical scores (Mini‐Mental State Examination [MMSE], Clinical Dementia Rating [CDR]). All longitudinal data were selected from the date closest in time to the corresponding clinical biomarker test, and only data within 2 years of the test were included.

2.3. AD biomarker testing

CSF biomarker positivity was based on clinical interpretation of the Roche Elecsys phosphorylated tau 181 (p‐tau181)/amyloid beta (Aβ) 42 ratio test (Generation I performed at the Mayo Clinic in Jacksonville, FL before June 2023 and Generation II performed at either the Mayo Clinic (between June 2023 and June 2024) or Washington University in Missouri after June 2024). 21

Amyloid PET scans were performed with florbetaben or florbetapir and interpreted visually as either positive or negative for cortical amyloid retention. Centiloid (CL) values are derived from standardized uptake value ratios (SUVRs) and provide a continuous measure of amyloid burden on a scale anchored at 0 for young controls and 100 for patients with mild to moderate AD dementia. For this study, CL quantification was performed retrospectively using MIM software, with each scan analyzed individually rather than through an automated processing pipeline. 22 For quantitative assessment of amyloid PET scans, a value of >20 CL was considered positive.

The C2N Diagnostics PrecivityAD2 blood test has been routinely used at the MDC since July 2023. It utilizes a proprietary mass spectrometry platform measuring the p‐tau217/non‐phosphorylated‐tau217 ratio and the Aβ42/40 ratio in plasma to generate the APS2 score. 23

2.4. Timing analyses

The door‐to‐needle time was defined as the time from first clinic visit until the first lecanemab infusion and includes the time from first clinic visit until the first biomarker test and the time from first biomarker test until the first lecanemab infusion. Only patients who received their first biomarker test after US Food and Drug Administration approval of lecanemab (July 6, 2023) were included in the door‐to‐needle‐time analysis. The last MDC visit date before the date of first biomarker testing was treated as the baseline visit for this analysis.

2.5. Statistical analysis and data visualization

To evaluate for differences in continuous variables, Mann‐Whitney U tests were used for comparisons between two groups and Kruskal‐Wallis tests for comparisons between multiple groups. Spearman correlations examined continuous biomarker relationships. Logistic regression analyses were performed to determine whether patients treated with lecanemab were more likely to undergo multiple biomarker tests and whether intermediate plasma p‐tau217 ratio values were more likely to be associated with multiple biomarker testing. Statistical analyses and data visualization were performed using R studio (version 4.3.1) and GraphPad Prism (version 10.4.0).

2.6. Ethics

The study was approved by the Washington University Institutional Review Committee. It was performed in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

2.7. Data access and availability

Because data in this study were from the health records of clinic patients who have not consented to data sharing, individual‐level clinical data are not readily sharable. However, anonymized data derived from MDC EHRs can be requested from https://i2db.wustl.edu/consultation‐services/.

3. RESULTS

3.1. Cohort characteristics

Between July 2021 and March 2025, 1054 unique patients underwent at least one AD biomarker test at MDC (Table 1; see Table S1 for stratification by single versus multiple biomarker testing status). The median age was 73.0 years, 52% were female, and 94% were White. Most patients (79%) had mild cognitive impairment (MCI) or very mild dementia (CDR = 0.5), and 18% had mild, moderate, or severe dementia (CDR ≥ 1). Further, 10.5% had a history of chronic kidney disease (CKD), the median creatinine was 0.92 mg/dL, median estimated glomerular filtration rate (eGRF) was 74 mL/min/1.73 m2, 75.9% had an eGFR > 60 mL/min/1.73 m2, and 4.5% had an eGFR < 40 mL/min/1.73 m2. The median BMI was 25.9 kg/m2 (overweight). Of these individuals who underwent biomarker testing, 272 (26%) initiated treatment with lecanemab.

TABLE 1.

Cohort characteristics.

Characteristic Number of observations Values
Age (years) 1054 73.0 (68.2 to 78.2)
Sex (female) 1054 543 (51.5%)
Race 1038
White 977 (94.1%)
Black 48 (4.6%)
Other 13 (1.3%)
Ethnicity (non‐Hispanic) 1027 1015 (98.8%)
Lecanemab treatment status 1054 272 (25.8%)
BMI (kg/m2) 501 25.9 (22.9 to 29.7)
MMSE score 947 25 (22‐27)
CDR global score 903
0 21 (2.3%)
0.5 715 (79.1%)
≥1 167 (18.5%)
CKD status 989 104 (10.5%)
Creatinine (mg/dL) 437 0.92 (0.80 to 1.14)
eGFR (mL/min/1.73 m2) 381 74 (61 to 86)
eGFR > 60 mL/min/1.73 m2 289 (75.9%)
eGFR > 40 < 60 mL/min/1.73 m2 75 (19.7%)
eGFR < 40 mL/min/1.73 m2 17 (4.5%)
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Note: The available data on 1054 included individuals is shown. Age, laboratory values, BMI, and cognitive scores were selected at the time of first biomarker test. Some individuals did not identify as Black or White. Information on ethnicity, BMI, comorbidities, laboratory values, and cognition was not available for every individual. Counts and percentages are provided for categorical variables. Median and interquartile range are indicated for continuous variables. CKD, Chronic Kidney Disease; BMI, Body Mass Index; eGFR, Estimated Glomerular Filtration Rate; MMSE, Mini Mental State Examination; CDR, Clinical Dementia Rating.

3.2. Biomarker testing volume

The number of biomarker tests of each modality is depicted in Figure 1a for the entire 1054 patients: 419 (40%) patients received an amyloid PET scan only, 456 (43%) a CSF test only, and 132 (13%) a blood test only. A small number of patients, 47 out of 1054 (4%), underwent testing with more than one biomarker modality: 24 (2%) patients received an amyloid PET and CSF test, 12 (1%) a CSF and blood test, nine (1%) an amyloid PET and blood test, and two (< 1%) an amyloid PET, CSF, and blood test.

FIGURE 1.

FIGURE 1

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Number of biomarker tests of each modality. (A) Entire cohort and (B) lecanemab‐treated subcohort.

The use of biomarker modalities was comparable for the lecanemab‐treated subcohort of 272 patients (Figure 1b): 90 (33%) patients underwent an amyloid PET only, 126 (46%) a CSF test only, and 39 (14%) a blood test only. Only 17 patients underwent multiple tests: six (2%) an amyloid PET and CSF test, seven (3%) a CSF and blood test, three (1%) an amyloid PET and blood test, and one (< 1%) an amyloid PET, CSF, and blood test.

3.3. Rates of positivity and concordance between modalities

The overall rate of biomarker positivity was 70%. Amyloid PET and CSF tests agreed in 20 of 26 patients (77%), CSF tests and blood tests agreed in 14 of 14 patients (100%), and amyloid PET and blood tests agreed in nine of 11 patients (82%). Confusion matrices for blood test results against amyloid PET (Table 2a) and CSF test results (Table 2b) revealed that of the 17 patients with positive blood test results, all 17 were positive by either amyloid PET (n = 8) or CSF tests (n = 9), i.e., no false positive blood test results were detected.

TABLE 2.

Confusion matrices for blood against amyloid PET and CSF tests. For amyloid PET, visual read was used as the reference standard.

Blood tests
Positive Negative Total
(A) Blood versus amyloid PET
Amyloid PET
Positive 8 2 10
Negative 0 1 1
Total 8 3 11
(B) Blood versus CSF tests
CSF
Positive 9 0 9
Negative 0 5 5
Total 9 5 14
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3.4. Multiple biomarker testing by treatment status and blood test results

Multiple biomarker tests were performed in 17 out of 272 (6.0%) patients treated with lecanemab and in 30 out of 782 (3.8%) untreated patients. Treated patients were not significantly more likely to undergo multiple biomarker testing compared to untreated patients (odds ratio [OR] = 1.7 [95% confidence intervals [CI] 0.91 to 3.10], p = 0.099).

All 50 patients treated with lecanemab with blood test results had a plasma p‐tau217 ratio above the clinically used cut‐off value of 4.2% 19 (Figure 2). Based on previously established cut‐offs to define a range of intermediate values (3.93% to 5.18%) for the plasma p‐tau217 ratio, 13 nine individuals with a blood test had intermediate values. Individuals with intermediate plasma p‐tau217 ratios were not significantly more likely to undergo multiple biomarker testing (OR = 0.70, 95% CI = 0.08 to 5.91, p value = 0.74).

FIGURE 2.

FIGURE 2

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Plasma p‐tau217 ratio and multiple biomarker testing, stratified by treatment status. Red dots represent patients who underwent blood testing only; additional colors indicate patients who received additional biomarker testing with amyloid PET and/or a CSF test. The dashed line represents the clinically used cut‐off value of 4.2%.

3.5. Correlation between continuous biomarker values

The continuous relationships of the plasma p‐tau217 ratio with amyloid PET CL and CSF p‐tau181/Aβ42 were evaluated. In 11 individuals (10 amyloid PET CL positive [> 20 CL] and one amyloid PET CL negative [≤20 CL]), there was no significant correlation between plasma p‐tau217 ratio with amyloid PET CL (Figure 3a). However, in 14 individuals (nine CSF positive and five CSF negative), there was a strong correlation (Spearman's ρ = 0.82) between continuous blood and CSF p‐tau181/Aβ42 (Figure  3b ).

FIGURE 3.

FIGURE 3

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Correlations of plasma p‐tau217 ratio with amyloid PET CL and CSF p‐tau181/Aβ42. Scatterplots show (A) p‐tau217 ratio versus amyloid PET CL or (B) CSF p‐tau181/Aβ42. The dashed lines indicate clinically used thresholds: 20 CL for amyloid PET CL, slightly different values for the three CSF test versions (0.23 for Elecsys Generation I and 0.28 for Elecsys Geneneration II performed at either Mayo Clinic, Jacksonville, FL, or Washington University), and 4.2% for the plasma p‐tau217 ratio. Point colors indicate the CSF test version and amyloid PET status by visual read; point shapes indicate lecanemab treatment status.

3.6. Influence of biomarker testing on the door‐to‐needle time for lecanemab treatment

For this substudy, n = 221 patients were identified who underwent AD biomarker testing between July 6, 2023, to March 1, 2025, and subsequently initiated lecanemab treatment (Figure 4).

FIGURE 4.

FIGURE 4

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Door‐to‐needle time for lecanemab treatment. The overall door‐to‐needle‐time is the time from first clinic visit until first biomarker test (left) and the time from first biomarker test until first lecanemab infusion (right). Time periods are shown in median months according to each modality and for multiple versus single biomarker testing. For multiple biomarker testing, the sequence of performed modalities is shown. The arrow length corresponds to the time interval. Bars and asterisks indicating statistical significance: **p < 0.01; ***p < 0.001.

For patients who underwent single‐biomarker testing, the time from first clinic visit to first infusion (door‐to‐needle time) varied by the modality performed (p = 0.002): amyloid PET, 4.0 months (interquartile range [IQR] 2.3 to 5.3); CSF test, 5.5 months (IQR 3.7 to 7.6); blood test, 4.9 months (IQR 3.4 to 7.3).

The time from first clinic visit to first biomarker test varied by modality (p < 0.01): amyloid PET, 1.1 months (IQR 0.7 to 1.7); CSF test, 1.8 months (IQR 0.8 to 2.9); blood test, 1.2 months (IQR 0.7 to 1.9). The time from first biomarker test to the first lecanemab infusion also varied by modality (p = 0.0004): amyloid PET, 2.9 months (IQR 2.1 to 3.6); CSF test, 3.7 months (IQR 2.8 to 4.8); blood test, 3.7 months (IQR 2.7 to 5.5).

The time from first test until first infusion was approximately twice as long in the case of multiple biomarker testing (6.1 months [IQR 3.8 to 7.8]) compared to the performance of a single modality (3.3 months [IQR 2.4 to 4.5]) (p < 0.001). Accordingly, the overall door‐to‐needle time was longer for patients who underwent multiple biomarker tests compared to single‐biomarker testing (p = 0.002): multiple biomarker tests, 8.1 months (IQR 6.1 to 10.5); single biomarker test, 4.7 months (IQR 3.1 to 6.7). Inspection of the sequence of multiple biomarker tests and clinical review suggests that the most common reason (seven out of 12, 58%) for ordering a second test was uncertainty in CSF test results, such as a low CSF Aβ42 but normal p‐tau181 and total tau values, or vice versa, or borderline CSF ratios. The single patient who underwent all three biomarker modalities had later CSF testing performed for an alpha‐synuclein seeding assay to rule‐out dementia with Lewy bodies.

4. DISCUSSION

The first aim of this study was to investigate the concordance of AD blood biomarker tests with amyloid PET and CSF test results in a real‐world setting. In our clinic cohort, which had a limited sample size, we found high concordance between the PrecivityAD2 blood test results and amyloid PET (nine of 11) or CSF tests (14 of 14). Importantly, no false positive blood test results were found; however, only 17 patients had positive blood tests. The second aim of the study was to examine the time from the first clinic visit until lecanemab treatment initiation for patients undergoing a single versus multiple biomarker tests. Performing multiple biomarker tests increased the time from first biomarker test until first lecanemab infusion from approximately 3 to 6 months, thus prolonging the overall door‐to‐needle time from less than 5 months to approximately 8 months.

There was a strong correlation between absolute biomarker values in CSF and blood (n = 14), but not between amyloid PET CL values and plasma p‐tau217 ratio (n = 11). The lower rate of concordance and weaker correlation of amyloid PET (compared to CSF) with blood test results is likely due to multiple reasons. First, in addition to the larger sample size for CSF comparisons there was greater balance between biomarker positive and negative individuals for CSF tests compared to PET, which increases associations with the plasma p‐tau217 ratio. 9 Additionally, amyloid PET and blood tests differ concerning the underlying pathobiological component that they reflect, i.e., amyloid PET visualizes the lifetime accumulation of amyloid in the brain, whereas fluid biomarkers reflect the equilibrium of certain analytes at a given time point. 15 Notably, amyloid PET (visual read) and CSF are typically discordant in approximately 10% of patients. 5 , 24 Finally, inconsistency between amyloid PET visual read and CL quantification may further complicate the relationship between amyloid PET imaging and fluid biomarker modalities. A recent PET study reported discordance between visual read and CL quantification in up to 14% of cases. 25

The cumulative door‐to‐needle time was at least 4 months for all three biomarker modalities. Health systems may benefit from tracking this information to find bottlenecks and optimize care pathways. In the MDC, amyloid PET was performed fastest, and CSF testing was performed slowest, likely because of the high imaging capacity at Washington University, which is not representative of less specialized and/or non‐academic centers within the United States or most clinical settings outside the United States. At the MDC, patients still must visit a designated AD blood draw clinic rather than being sent to the clinical lab immediately after their MDC visit due to administrative issues. Also, the corresponding report form is not digitized yet, which may lead to delayed return of results. With changes to administrative processes, AD blood testing has the potential to become the fastest biomarker modality given their potential to be performed at the initial visit. In Europe, where CSF testing is the dominant AD biomarker modality, 26 CSF testing may be performed more quickly than at MDC. However, recent literature from Europe suggests that a shift from CSF to blood testing may increase access to biomarker testing. 27 Given the relatively high burden of lumbar punctures for providers and patients, CSF testing could be used in a targeted manner in patients with diagnostic uncertainty after blood tests. 28

Performing multiple biomarker tests nearly doubled the time from first biomarker test to the initial lecanemab infusion, increasing the overall door‐to‐needle time by 3.4 months, from 4.7 to 8.1 months. There was a trend toward multiple biomarker tests being more frequently performed in patients treated with lecanemab compared to untreated patients, although this was not statistically significant. Still, due to time delays, multiple biomarker testing may lead to avoidable disease progression and reduced treatment efficacy in these patients. For instance, projected wait times for AD diagnosis in some European countries could reach approximately 50 months due to very limited amyloid PET capacity, but they may be greatly reduced by including blood tests in the diagnostic process. 29 , 30 , 31 , 32 To reduce the need for additional biomarker testing, it may be reasonable to perform a second test in select cases: patients with a low pretest probability (e.g., younger patients or those with atypical or complex syndromes) or intermediate blood test results.

In our cohort, multiple biomarker testing was not significantly associated with intermediate plasma p‐tau217 ratios, although very few patients had intermediate blood biomarker levels. Instead, ambiguous CSF test results were the most common reason for the performance of a second biomarker test in our cohort. CSF testing is particularly well suited for investigating more complex cases, such as suspected alpha‐synucleinopathies. 33 On the other hand, CSF biomarkers may be affected by CSF flow abnormalities such as normal pressure hydrocephalus. 34 It is possible that patients who underwent multiple biomarker tests represented clinically more complex cases with lower diagnostic certainty. Therefore, multiple biomarker tests and a longer time until diagnosis may be necessary in some cases to increase diagnostic certainty and to prevent inappropriate ATT use.

This is a preliminary study, and the results should be further validated as AD blood tests become more established in clinical practice. A major limitation is the small sample of patients undergoing multiple biomarker testing, which affects statistical robustness and could impact generalizability of these results. Further, the rates of agreement between different modalities may vary for different AD blood tests. 35 CKD has been associated with increased p‐tau217 concentrations in plasma, which is mitigated by use of %p‐tau217, a component of the PrecivityAD2 test. 36 , 37 Still, there may be limitations for the utility of AD plasma tests in individuals with significant renal impairment (eGFR < 45 mL/min/1.73 m2), which can be easily identified with routine blood work. Notably, the rate of moderate to severe CKD was low (<5%) within our cohort, suggesting that blood tests may be used in most memory clinic patients. Additionally, our cohort was >90% non‐Hispanic White, and the biomarker results may not be transferable to more ethno‐racially diverse cohorts due to reported differences in biomarker performance and positivity rates depending on racial differences. 38

For the timing analyses, we did not consider the potential influence of other factors within the diagnostic workup, such as APOE genotyping, neurocognitive testing, or magnetic resonance imaging (MRI), which are mandatory steps during evaluation for ATT eligibility. There may be significant bottlenecks in access to MRI in non‐academic settings and countries besides the United States, 39 and therefore it might influence the door‐to‐needle time for ATTs. Thus, the observed delays for multiple biomarker testing reported in our study might be confounded by this overall diagnostic complexity. However, these effects would likely apply to all biomarker modalities and single as well as multiple testing. Future analyses with greater sample sizes and statistical power should consider these factors using multivariable analyses. Additionally, approximately 80% of our patients had a baseline CDR of 0.5 corresponding to either MCI or very mild dementia. While it is critical to diagnose AD and initiate ATT in the earliest stages of disease, 18 this distribution may not be representative of other sites, and diagnostic challenges in patient cohorts with more advanced cognitive impairment (CDR 1+) might lead to results different from our own.

In summary, the PrecivityAD2 blood test was able to detect amyloid pathology with high accuracy in this real‐world cohort, with no false positive cases. Biomarker modalities should be carefully selected for each individual based on practical and patient‐specific factors. 15 Clinicians should be aware that performing multiple biomarker tests may delay initiation of disease‐modifying treatments and therefore should perform multiple biomarker tests in cases where it is likely to add value to the clinical decision‐making process.

CONFLICT OF INTEREST STATEMENT

AH has received research funding from Novo Nordisk and has collaborated with Biogen on a research project. MP reported personal fees from an Eisai honorarium of less than $500 received for participating in scientific board meetings and serving as subinvestigator on sponsored clinical trials from Eisai and Eli Lilly outside the submitted work. MRP has received fees from CLARiTI U01 AG092350, NACC U24 AG072122, Avid Radiopharmaceuticals, Inc., and Lantheus Medical Imaging, Inc. She has served as a board officer/chair for the American Board of Nuclear Medicine. WP has received research funding from Novo Nordisk. TB reported grants from Siemens, loan of equipment from Hyperfine, precursors and technology transfer from Lantheus Radiopharmaceutical and Eli Lilly/Avid Radiopharmaceuticals, personal fees from Biogen, Eli Lilly, Eisai, Bristol Myers Squibb, Johnson & Johnson, and Merck, and payment for the generation of medical education activities from Medscape, PeerView, and Neurology Today outside the submitted work. JCM is funded by National Institutes of Health (NIH) grant nos. P30 AG066444, P01AG003991, and P01AG026276. Neither Dr. Morris nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. JS reported advisory board fees and grants from Eisai and Eli Lilly outside the submitted work. SES has not received any financial compensation from pharmaceutical or diagnostics companies since 2024, when she received honoraria for serving on scientific advisory boards on biomarker testing and education for Eisai and Novo Nordisk and speaking fees from Eisai, Eli Lilly, and Novo Nordisk. She has recently received honoraria for educational presentations from Medscape, PeerView, and the Academy for Continued Healthcare Learning. She has provided unpaid scientific advising to Acumen, Biogen, Cognito Therapeutics, Danaher, Eisai, Eli Lilly, Johnson & Johnson Innovative Medicine, Sanofi, and Siemens. Washington University has a stake in C2N Diagnostics. Declarations of interest: none for all other authors. Author disclosures are available in the Supporting Information.

CONSENT STATEMENT

Informed consent was not necessary for this study.

Supporting information

Supporting Information: dad270387‐sup‐0001‐tableS1.docx

DAD2-18-e70387-s001.docx (20.5KB, docx)

Supporting Information: dad270387‐sup‐0002‐SuppMat.pdf

DAD2-18-e70387-s002.pdf (2.3MB, pdf)

ACKNOWLEDGMENTS

We thank our clinic patients and their supportive families. At Washington University MDC we would like to thank all the clinicians (Erik Musiek, David Holtzman, Randall Bateman, Eric McDade, Jee‐Young Han, David Carr, Steven Dunham, Nupur Ghoshal, Justin Long, Cassandra Ward, and Kyle Womack) and nursing staff (Dawn Ellington, Zachary Posey, Maria Carroll, Erica Woolfolk). Funding for this study was from start‐up gift funds to SES from the Barbara Morriss trust. The study funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. AH and SES had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Contributor Information

Anna Hofmann, Email: anna.hofman@wustl.edu.

Suzanne E. Schindler, Email: schindler.s.e@wustl.edu.

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