What the research actually found

1. Benefit meta-analysis 2025

   Diagnostic accuracy of phosphorylated tau217 in detecting Alzheimer's disease pathology among cognitively impaired and unimpaired: A systematic review and meta-analysis

   Outcome measured: Sensitivity and specificity for amyloid and tau PET positivity (pooled)

   Plasma p-tau217 showed 82% sensitivity for detecting amyloid and 83% for tau, with 86% and 83% specificity, respectively. CSF p-tau217 had 79% sensitivity for amyloid and 91% for tau, with 91% and 84% specificity

   Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217 detected amyloid PET positivity with 82% sensitivity and 86% specificity, comparable to CSF p-tau217; less sensitive for tau PET.

2. Benefit meta-analysis n=29,625 2025

   Blood phosphorylated tau for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis

   Outcome measured: Pooled sensitivity, specificity and AUROC for biologically defined Alzheimer's disease

   Plasma p-tau217 was the highest-performing biomarker for identifying biologically defined Alzheimer's disease, with pooled sensitivity of 88·1% (95% CI 86·7-89·5, moderate certainty of evidence), specificity of 88·7% (87·4-89·9, moderate certainty of evidence), area under the receiver operating characteristic curve (AUROC) of 91·1% (88·9-92·4, moderate certainty of evidence), and diagnostic odds ratio of 50·7 (40·6-63·4). p-tau181 pooled sensitivity was 80·5% (78·4-82·4, low certainty of evidence), specificity was 76·4% (74·1-78·6, low certainty of evidence), AUROC was 81·5% (80·2-82·9, low certainty of evidence)

   Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217 was the best-performing marker (88.1% sensitivity, 88.7% specificity, AUROC 91.1%, moderate certainty), ahead of p-tau181 and p-tau231; about 90% of studies were at high risk of bias.

3. Mixed meta-analysis 2025

   Blood-based biomarkers for detecting Alzheimer's disease pathology in cognitively impaired individuals within specialized care settings: A systematic review and meta-analysis

   Outcome measured: Pooled sensitivity and specificity of 31 blood-based biomarker tests for Alzheimer pathology in cognitively impaired people

   the pooled sensitivity ranged from 49.3% (95% confidence interval [CI]: 41.2-57.4) to 91.4% (95% CI: 86.6-94.6), and the pooled specificity ranged from 61.5% (95% CI: 45.6-75.3) to 96.7% (95% CI: 87.8-99.2)

   Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Performance varied widely across tests, from 49.3% to 91.4% pooled sensitivity and 61.5% to 96.7% pooled specificity at a single cut-point, with most studies at high risk of bias.

4. No effect phase 3 trial n=830 2026

   Plasma P-tau217 for detecting amyloid clearance after donanemab in Alzheimer's disease

   Outcome measured: Detection of PET-confirmed amyloid clearance after donanemab (AUC at 52 weeks)

   Plasma p-tau217 showed suboptimal performance in detecting TRAC by PET in donanemab-treated participants (N = 830), with an area under the ROC curve of 0.61 at 52 weeks

   Direction is for the blood test's ability to detect treatment-related amyloid clearance on PET: AUC 0.61, which the authors call suboptimal and not currently usable for that purpose. It says nothing about the drug's effect.

5. Mixed systematic review 2026

   Cost-effectiveness of testing biofluid biomarkers to diagnose Alzheimer's disease: a systematic review

   Outcome measured: Cost-effectiveness of CSF and blood biomarker testing for AD diagnosis across nine model-based economic evaluations

   The review's own summary points two ways: CSF biomarker tests were mostly cost-effective against cognitive assessment or imaging, while blood biomarker tests showed mixed results; every included study was model-based.

6. No direction reported systematic review 2025

   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

   Outcome measured: None measured (clinical practice guideline)

   A clinical practice guideline. It sets performance thresholds for blood tests (at least 90% sensitivity and 75% specificity for triage; at least 90% for both to substitute for amyloid PET or CSF) and reports no effect estimate of its own.

7. Benefit cohort study n=572 2026

   Integration of plasma eMTBR-tau243 and p-tau217 in the diagnosis and stratification of Alzheimer's disease: a prospective cohort study

   Outcome measured: Classification of established Alzheimer's disease by plasma eMTBR-tau243 among %p-tau217-positive patients

   194 (55%) of 350 %p-tau217-positive patients were also positive for eMTBR-tau243, with an accuracy of 81% (95% CI 76-84), PPV 84% (95% CI 78-88), negative predictive value (NPV) 77% (95% CI 68-82), and sensitivity 82% (95% CI 76-87) for established Alzheimer's disease, in cross-sectional analyses

   Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Among p-tau217-positive patients, a positive eMTBR-tau243 identified clinically established Alzheimer's disease with 81% accuracy and predicted faster cognitive decline and tau accumulation.

8. Benefit cohort study n=998 2025

   A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests

   Outcome measured: Accuracy of five plasma p-tau217 tests for amyloid PET and tau PET status, benchmarked against CSF tests

   All plasma p-tau217 tests exhibited a high ability to detect abnormal Aβ-PET [area under the curve (AUC) range: 0.91-0.96] and tau-PET (AUC range: 0.94-0.97) ... For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 0.91 (immunoassays: 0.84-0.87) and a specificity of 0.94 (immunoassays: 0.85-0.89)

   Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. All p-tau217 tests detected abnormal amyloid PET (AUC 0.91-0.96) and tau PET (0.94-0.97); the mass-spectrometry %p-tau217 ratio was best (accuracy 0.93 versus 0.83-0.88 for immunoassays) and is proposed as a stand-alone confirmatory test, with immunoassays better suited to triage.

9. Benefit cohort study n=786 2024

   Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

   Outcome measured: Accuracy for abnormal amyloid and tau pathology (PET or CSF) and longitudinal change

   High accuracy was observed in identifying elevated Aβ (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal Aβ pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%

   Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The ALZpath plasma p-tau217 immunoassay reached AUC 0.92-0.96 for amyloid and 0.93-0.97 for tau across three cohorts, comparable with CSF, and a three-range cut-off cut confirmatory testing by about 80%.

10. Benefit cohort study n=912 2024

    Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies

    Outcome measured: Identification of amyloid positivity and of high tau-PET load (to select candidates for anti-amyloid antibodies)

    plasma p-tau217 was most strongly associated with Aβ positivity (test-set area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI, 0.90-0.97) ... This procedure had an overall sensitivity of 0.94 (95% CI, 0.90-0.98) and a specificity of 0.86 (95% CI, 0.77-0.95) ... At a false-negative rate less than 10%, the use of plasma p-tau217 could avoid 56.9% of tau-PET scans needed to identify high tau PET among Aβ-positive participants

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217 identified amyloid positivity with AUC 0.94; a two-cut-point rule sent only 17% for CSF or PET (sensitivity 0.94, specificity 0.86), and among amyloid-positive people it identified high tau load (AUC 0.92), potentially avoiding 56.9% of tau-PET scans.

11. Benefit cohort study n=348 2023

    A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases

    Outcome measured: Accuracy for amyloid PET status and reduction in confirmatory CSF tests with a two-step plasma p-tau217 workflow

    Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting Aβ-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. A blood model of p-tau217, age and APOE ε4 (AUC 89.3% development, 94.3% validation) used to triage patients gave 88-92% overall accuracy while cutting confirmatory CSF tests by 61-86%.

12. Benefit cross-sectional study n=344 2026

    Head-to-head comparison of plasma p-tau217 immunoassays for incipient Alzheimer's disease in community cohorts

    Outcome measured: Cross-assay agreement and AUC for amyloid PET positivity across four p-tau217 immunoassays

    All four p-tau217 assays exhibited moderate to strong cross-platform correlations (Spearman correlations of 0.40–0.86), and statistically equivalent AUCs (of 0.84–0.90) for determining Aβ positivity

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. All four assays (Lumipulse, Johnson & Johnson, ALZpath, NULISA) gave statistically equivalent AUCs of 0.84-0.90 for amyloid positivity, with cross-platform correlations of 0.40-0.86.

13. Benefit cross-sectional study n=2,571 2026

    Plasma Phosphorylated Tau 217 Cutoffs for Amyloid Pathology and Kidney Function, Body Mass Index, and Anemia

    Outcome measured: Accuracy of plasma p-tau217 for amyloid PET positivity under standard, subgroup-optimal and double cutoffs in people with kidney disease, abnormal BMI or anaemia

    In the UGOT cohort, the optimal cutoff improved diagnostic accuracy compared with the standard single cutoff, particularly in CKD and anemia (CKD: from 0.65; 95% CI, 0.57-0.72; to 0.83; 95% CI, 0.76-0.89; anemia: from 0.80; 95% CI, 0.76-0.84; to 0.86; 95% CI, 0.82-0.90), with consistent findings in the Roche cohort

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Subgroup-specific optimal cutoffs and a double-cutoff strategy both improved accuracy over the standard single cutoff, most markedly in chronic kidney disease (0.65 to 0.83) and anaemia.

14. Mixed cross-sectional study n=617 2026

    Electronic Health Records to Test Multimorbidity Influences to Plasma Biomarker Interpretation for Alzheimer's Disease

    Outcome measured: Associations of plasma p-tau217, Aβ42/40 and p-tau217/Aβ42 with AD-related factors and with medical comorbidities (kidney function, diabetes, hearing loss) in a health-system biobank

    The findings point two ways: the p-tau217/Aβ42 ratio tracked AD-related factors (MCI, AD dementia, future progression, age, APOE ε4) more closely than either marker alone and had few intermediate results, but it was also related to kidney function, diabetes and hearing loss, and medical morbidities were most frequent among intermediate classifications.

15. Benefit cross-sectional study n=191 2025

    Independent validation of the PrecivityAD2 blood test to identify presence or absence of brain amyloid pathology in individuals with cognitive impairment

    Outcome measured: Agreement with amyloid PET in an independent cohort (ADNI)

    Concordance with amyloid PET was high (AUC-ROC 0.95 (95% CI): 0.93-0.98); 54% of participants had a positive APS2. The previously validated APS2 cut point yielded an overall accuracy of 91% (95% CI: 86-94%), sensitivity 90% (95% CI: 83-94%) and specificity 92% (95% CI: 84-96%)

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The prespecified APS2 cut point gave 91% accuracy, 90% sensitivity and 92% specificity against amyloid PET.

16. Benefit cross-sectional study n=1,767 2025

    Plasma phospho-tau217 for Alzheimer's disease diagnosis in primary and secondary care using a fully automated platform

    Outcome measured: Diagnostic accuracy for Alzheimer pathology (CSF-defined) in secondary and primary care

    Plasma p-tau217 detected AD pathology with areas under the receiver operating characteristic curves of 0.93-0.96. In secondary care, the accuracies were 89-91%, the positive predictive values 89-95% and the negative predictive values 77-90%. In primary care, the accuracy was 85%, the positive predictive values 82% and the negative predictive values 88%. Accuracy was lower in participants aged ≥80 years (83%)

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. AUC 0.93-0.96; accuracy 89-91% in secondary care and 85% in primary care, lower (83%) at age 80 or older; a two-cutoff approach raised accuracy to 92-94% at the cost of 12-17% intermediate results.

17. Benefit cross-sectional study n=363 2025

    Pittsburgh plasma p-tau217: Classification accuracies for autosomal dominant and sporadic Alzheimer's disease in the community

    Outcome measured: Classification accuracy of a new p-tau217 assay against PSEN1 carrier status and amyloid PET

    Pitt-p-tau217 differentiated neuropathologically confirmed PSEN1 mutation carriers from controls with area under the curve (AUC) = 0.94, and amyloid beta (Aβ) positron emission tomography (PET)-positive from Aβ PET-negative cognitively normal older adults with AUC up to 0.84, equivalent to ALZpath-p-tau217 results. Both Pitt-p-tau217 and ALZpath-p-tau217 were slightly elevated in tau PET-positive versus tau PET-negative participants. Between-assay correlations were up to 0.93

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The Pitt-p-tau217 assay separated PSEN1 carriers from controls (AUC 0.94) and amyloid PET-positive from -negative cognitively normal adults (AUC up to 0.84), equivalent to the ALZpath assay.

18. Benefit cross-sectional study n=512 2025

    Diagnostic accuracy of plasma p-tau217/Aβ42 for Alzheimer's disease in clinical and community cohorts

    Outcome measured: Diagnostic accuracy for abnormal amyloid PET and tau PET in a clinic and a community cohort

    Plasma p-tau217/Aβ42 exhibited high performance for abnormal statuses of Aβ PET (area under the curve [AUC]: 0.963 to 0.966) and tau PET (AUC: 0.947 to 0.974) ... The p-tau217/Aβ42 ratio had a lower intermediate percentage than p-tau217 alone in both clinic (10.6% vs 13.0%) and community (16.5% vs 31.4%) cohorts

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The Lumipulse plasma p-tau217/Aβ42 ratio reached AUC 0.963-0.966 for amyloid PET and 0.947-0.974 for tau PET, equivalent to CSF tests and better than plasma p-tau217 alone, with fewer intermediate results.

19. Benefit cross-sectional study n=1,135 2025

    Comparison of plasma p-tau217/Aβ42, p-tau217, and Aβ42/Aβ40 biomarkers by race to detect Alzheimer's disease

    Outcome measured: Accuracy for amyloid PET positivity in people who self-identify as Black or White

    In the test set, plasma p-tau217/Aβ42 had the highest accuracy (pBlack: 0.88, pWhite: 0.91) and lowest proportion of intermediate classifications (≤0.16), with no classification difference by race (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.66-2.95, p = 0.33)

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217/Aβ42 had the highest accuracy (0.88 in Black and 0.91 in White participants) and fewest intermediate results, with no difference in classification by race.

20. Harm cross-sectional study n=202 2025

    Quantitative Assessment of the Effect of Chronic Kidney Disease on Plasma P-Tau217 Concentrations

    Outcome measured: Plasma p-tau217 concentration by kidney function (eGFR) in amyloid-negative and amyloid-positive people

    For an eGFR of 45 vs 60 in the A- cohort, the calculated percentage changes were +31%, +55%, and +19%, for ALZpath p-tau217, C2N p-tau217, and C2N %p-tau217, respectively. For the A+ cohort, the corresponding calculated percentage changes were +17%, +15%, and -5%, respectively

    Direction is for chronic kidney disease as a source of false signal: at eGFR 45 versus 60, p-tau217 was 31-55% higher in amyloid-negative people on two immunoassays, a rise largely removed by using the %p-tau217 ratio. A test-validity result, not a health outcome.

21. Benefit cross-sectional study n=509 2025

    Diagnostic performance of plasma p-tau217 and Aβ42/40 biomarkers in the outpatient memory clinic

    Outcome measured: Sensitivity and specificity for symptomatic AD, and agreement with CSF biomarkers, in a tertiary outpatient memory clinic

    Plasma p-tau217 distinguished patients with diagnoses of symptomatic AD with 95% sensitivity and 82% specificity. Integration of Aβ42 measurements (p-tau217/Aβ42) incrementally improved specificity (86%). Plasma p-tau217 and p-tau217/Aβ42 concentrations closely associated with established CSF biomarkers of AD (area under the curve [AUC]: 0.94 and 0.96, respectively)

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217 identified symptomatic AD with 95% sensitivity and 82% specificity (86% with the Aβ42 ratio) and tracked CSF biomarkers closely (AUC 0.94-0.96); reduced kidney function raised levels in patients without AD.

22. Benefit cross-sectional study n=1,213 2024

    Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care

    Outcome measured: Diagnostic accuracy for Alzheimer pathology (CSF-defined), and for clinical AD versus physicians' assessment

    the AUC was 0.97 (95% CI, 0.95-0.99) when the APS2 was used, the PPV was 91% (95% CI, 87%-96%), and the NPV was 92% (95% CI, 87%-96%) [primary care, single batch]; Primary care physicians had a diagnostic accuracy of 61% (95% CI, 53%-69%) for identifying clinical AD after clinical examination, cognitive testing, and a computed tomographic scan vs 91% (95% CI, 86%-96%) using the APS2. Dementia specialists had a diagnostic accuracy of 73% (95% CI, 68%-79%) vs 91% (95% CI, 88%-95%) using the APS2

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The APS2 blood test reached AUC 0.96-0.97 and 88-92% accuracy, and its 91% accuracy for clinical AD beat primary care physicians (61%) and dementia specialists (73%).

23. Benefit cross-sectional study n=583 2024

    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

    Outcome measured: Agreement with amyloid PET (brain amyloidosis)

    The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET

    Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. APS2 gave AUC 0.94 and 88% agreement with amyloid PET, with similar performance by ethnicity, sex, age and APOE4 status.

24. No direction reported modelling study 2025

    Estimation of the value-based price of a blood test for Alzheimer's disease pathology in primary and specialty care in the U.S

    Outcome measured: Value-based price of a blood test for AD pathology as a triage or confirmatory test in primary and specialty care, and projected reduction in PET/CSF use

    If used in primary care, the value-based price would be $290 for a triage and $1150 for a confirmatory test, respectively, as use of PET or CSF testing would decline by 47 % and 86 %, respectively. If used in specialty care, i.e., after confirmation of early-stage cognitive impairment, the overall number of blood tests would decline. Consequently, the value-based price would increase to $450 for a triage test and $1950 for a confirmatory test

    A price-threshold model: it estimates the test price at which diagnostic cost per true-positive case equals standard care ($290-$1,950 depending on use), and compares no actual price against it, so there is no direction to record.

25. No direction reported None 2026

    FDA approval of the Lumipulse G pTau217/β-amyloid 1-42 plasma ratio test: a new era in accessible Alzheimer's diagnosis

    Outcome measured: None measured (editorial on the FDA clearance)

    FDA approval was based on clinical evidence showing strong agreement between plasma test results and confirmation by PET or CSF testing, with over 90% consistency in those with positive findings. In contrast, these reference methods confirmed 97.3% of those with negative plasma results to be amyloid negative

    An editorial reviewing the FDA clearance of the Lumipulse plasma ratio test. It relays performance figures from the FDA summary and other studies and reports no data of its own.

26. No direction reported None 2024

    Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease

    Outcome measured: None measured (performance recommendations)

    A workgroup recommendations document. It sets target sensitivity and specificity for blood biomarker tests (≥90% / ≥85% for triage in primary care; ~90% / ~90% as a confirmatory test) and reports no data of its own.

1. Mixed meta-analysis n=20,342 2026

   Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease (Cochrane review)

   Outcome measured: ADAS-Cog and CDR-SB at 18 months; ARIA

   ADAS-Cog SMD -0.11 (95% CI -0.16 to -0.06); ARIA-E absolute risk difference +107 per 1,000

   A statistically detectable but very small cognitive effect (ADAS-Cog SMD -0.11) alongside 107 more cases of ARIA-E per 1,000. The reviewers' own conclusion is that removing amyloid does not seem to produce clinically meaningful effects — the sharpest disagreement in this table with how the individual trials were reported.

2. Mixed meta-analysis n=23,202 2024

   Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis

   Outcome measured: Cognitive and functional scales against the MCID; ARIA

   CDR-SB mean difference -0.18 (95% CI -0.34 to -0.03), below the MCID; ARIA-oedema NNH 9

   Benefits were statistically present but every one fell below the minimum clinically important difference, against a number needed to harm of 9 for ARIA-oedema. Agrees with the Cochrane review and not with the trial reports.

3. Harm systematic review 2026

   Amyloid-Related Imaging Abnormalities (ARIA) in Anti-Amyloid Therapies for Alzheimer's Disease: An Update from the Alzheimer's Association ARIA Workgroup

   Outcome measured: ARIA incidence and severity

   "ARIA-E and ARIA-H occurred in 12.6% and 17.3% of participants on lecanemab, respectively" (CLARITY-AD); "ARIA-E and ARIA-H occurred in 24% and 31% of participants on donanemab, respectively" (TRAILBLAZER-ALZ-2); APOE e4 homozygotes "may have ~2.5 to 5 times greater risk for incident ARIA-E and for ARIA-H"

   The review's subject is the harm itself: brain swelling and microbleeds caused by the drugs.

4. Benefit phase 3 trial 2026

   Clinical Meaningfulness of Donanemab in Early Symptomatic Alzheimer Disease: Data From the Randomized Phase 3 TRAILBLAZER-ALZ 2 Trial

   Outcome measured: Progression between disease stages and to needing in-home support

   HR 0.67 for MCI-to-mild-dementia progression; HR 0.50 for mild-to-moderate; HR 0.74 for progression to needing in-home support

   Prespecified and post hoc re-analyses of a trial already reported elsewhere, so this is not independent evidence.

5. Harm phase 3 trial n=3,030 2025

   Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease: Secondary Analysis of the TRAILBLAZER-ALZ and ALZ 2 Randomized Clinical Trials

   Outcome measured: ARIA-E and ARIA-H incidence

   ARIA-E 24.4% vs 1.9% placebo; symptomatic ARIA-E 5.8%; serious ARIA-E 1.5%

   Against placebo: ARIA-E 24.4% vs 1.9%. Risk tracks APOE4 status and baseline imaging.

6. Benefit phase 3 trial n=843 2025

   Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction

   Outcome measured: ARIA-E incidence at 24 weeks

   ARIA-E 13.7% (modified titration) vs 23.7% (standard) at 24 weeks

   Direction is for the slower titration schedule against standard dosing, on the drug's own side effect. Amyloid reduction was comparable.

7. Benefit phase 3 trial 2025

   Long-term safety and efficacy of lecanemab in early Alzheimer's disease: Results from the Clarity AD open-label extension study

   Outcome measured: Clinical decline over up to 36 months

   "ARIA rates were low after 6 months and not associated with long-term progression. Across clinical and HRQoL endpoints, lecanemab-treated participants continued to benefit through 36 months. Separation between early and delayed start was maintained between 18 and 36 months."

   An open-label extension: after 18 months everyone is on the drug, so the comparison is early-start versus delayed-start, not drug versus placebo.

8. Benefit phase 3 trial n=1,795 2023

   Lecanemab in Early Alzheimer's Disease

   Outcome measured: CDR-SB at 18 months

   Adjusted mean CDR-SB change 1.21 (lecanemab) vs. 1.66 (placebo); difference -0.45 (95% CI -0.67 to -0.23, P<0.001)

   Less decline than placebo, alongside infusion reactions and ARIA.

9. Benefit phase 3 trial n=1,736 2023

   Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial

   Outcome measured: iADRS at 76 weeks

   iADRS change at 76 weeks: -6.02 (95% CI -7.01 to -5.03) donanemab vs -9.27 (-10.23 to -8.31) placebo in the low/medium tau population (difference 3.25, 95% CI 1.88-4.62; P<.001), and -10.2 vs -13.1 in the combined population (difference 2.92, 95% CI 1.51-4.33). CDR-SB difference -0.67 (95% CI -0.95 to -0.40)

10. Benefit randomised trial n=41 2023

    Interim Phase 1 multiple ascending dose results for remternetug (LY3372993) in Alzheimer's disease

    Outcome measured: Amyloid PET clearance (surrogate)

    "On 2,800 mg, every participant dropped below the amyloid positivity threshold within three months"; "After six months, plaque was dose-dependently reduced in all cohorts"

    Phase 1 dose-finding. The outcome is amyloid clearance; no cognitive outcome was measured.

11. Mixed phase 3 trial n=3,285 2022

    Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer's Disease

    Outcome measured: CDR-SB at 78 weeks

    EMERGE: CDR-SB difference -0.39 vs. placebo (95% CI -0.69 to -0.09; P=.012); ENGAGE: CDR-SB difference +0.03 vs. placebo (95% CI -0.26 to 0.33; P=.833)

    Two identically designed trials disagreed: EMERGE met its primary endpoint, ENGAGE did not.

12. Benefit phase 2 trial n=13 2025

    Interim biomarker results for trontinemab, a novel Brainshuttle antibody in development for the treatment of Alzheimer's disease

    Outcome measured: Amyloid PET and CSF biomarkers (surrogate)

    3.6 mg/kg cohort: "-89 centiloids after 12 weeks (n=13), and -107 centiloids after 28 weeks (n=12)" on amyloid PET; at week 25 CSF "total tau, phosphorylated tau181, and neurogranin were reduced by 30%, 34%, and 29%, respectively"

    Phase Ib/IIa biomarker result in 13 people; no cognitive outcome measured.

13. No direction reported cohort study n=234 2025

    Lecanemab Treatment in a Specialty Memory Clinic

    Outcome measured: ARIA and infusion reactions in routine care

    ARIA 22%; symptomatic ARIA 5.7% overall, 27% in mild dementia vs 1.8% in MCI/very mild dementia

    A single-clinic safety series with no comparison group. It reports how often ARIA and infusion reactions happened in practice, which is useful, but it cannot estimate an effect of the drug in either direction.

14. No direction reported case-control study n=6 2026

    Clonal expansion of cytotoxic CD8⁺ T cells in lecanemab-associated ARIA

    Outcome measured: Peripheral CD8+ T-cell signature in lecanemab-associated ARIA

    Mechanistic multi-omic profiling of blood from three ARIA-positive patients and three matched controls on lecanemab. It describes a clonally expanded cytotoxic CD8+ T-cell signature and estimates no clinical effect.

15. Benefit regulatory decision n=1,736 2025

    Kisunla (donanemab) — EU Marketing Authorization (EPAR), following CHMP re-examination

    Outcome measured: iADRS at 18 months, in the APOE4-restricted group

    "after 18 months of treatment, the iADRs score worsened by 11 points in patients who received Kisunla and 13 points in those given placebo"

    An initial negative opinion was reversed on re-examination, with use restricted to APOE4 heterozygotes and non-carriers. The EPAR describes ARIA as affecting more than 1 in 10 people without giving a percentage.

16. Benefit regulatory decision n=1,736 2024

    FDA Approves Treatment for Adults with Alzheimer's Disease (Kisunla / donanemab-azbt)

    Outcome measured: iADRS and CDR-SB at week 76

    Week 76 differences from placebo: iADRS 2.92 (p<0.0001); ADAS-Cog13 -1.33 (p=0.0006); ADCS-iADL 1.70 (p=0.0001); CDR-SB -0.70 (p<0.0001)

17. No direction reported company announcement 2024

    Biogen to Realign Resources for Alzheimer's Disease Franchise (Aduhelm discontinuation)

    Outcome measured: None reported

    Corporate announcement discontinuing a product and terminating its confirmatory trial. It reports no clinical outcome, so no direction exists to record.

18. Mixed regulatory decision n=1,521 2024

    Leqembi Recommended for Treatment of Early Alzheimer's Disease (CHMP re-examination, reversing July 2024 refusal)

    Outcome measured: CDR-SB at 18 months and ARIA rates, in the APOE4-restricted group

    "After 18 months of treatment, patients treated with Leqembi had a smaller increase in CDR-SB score than those who received placebo (1.22 versus 1.75)"; "8.9% of those with only one or no copy of ApoE4 experienced ARIA-E, compared with 12.6% of all patients ... 12.9% of patients in the restricted population experienced ARIA-H compared with 16.9% of the broader population"; placebo figures 1.3% and 6.8%

    CHMP refused the drug, then on re-examination recommended it only for people with one or no APOE4 copy, where the ARIA rates are lower. Benefit on cognition and harm from ARIA in the same document, with the restriction as the regulator's way of balancing them.

19. Mixed regulatory decision 2023

    FDA Approves LEQEMBI (lecanemab-irmb) Under the Accelerated Approval Pathway for the Treatment of Alzheimer's Disease

    Outcome measured: Amyloid PET (surrogate marker); ARIA rates

    Approved on amyloid reduction (surrogate) while reporting higher ARIA rates than placebo; the notice reports no cognitive outcome.

20. Benefit regulatory decision n=1,795 2023

    FDA Converts Novel Alzheimer's Disease Treatment to Traditional Approval

    Outcome measured: CDR-SB (clinical progression) at 18 months

    "Leqembi demonstrated a statistically significant and clinically meaningful reduction of decline from baseline to 18 months on the primary endpoint, the Clinical Dementia Rating Scale Sum of Boxes score, compared to placebo" — the notice gives no numeric CDR-SB difference

21. No direction reported coverage determination 2022

    National Coverage Determination: Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer's Disease (NCD 200.3)

    Outcome measured: Coverage policy

    A coverage determination. It sets the conditions under which Medicare pays and reports no effect estimate.

22. Benefit regulatory decision 2021

    FDA Grants Accelerated Approval for ADUHELM (aducanumab) as the First and Only Alzheimer's Disease Treatment to Address a Defining Pathology of the Disease

    Outcome measured: Amyloid PET (surrogate marker)

    Benefit is on the surrogate marker only: the approval rested on amyloid reduction, not on confirmed clinical benefit, and the confirmatory trial was later terminated.

23. Benefit None 2026

    The Alzheimer's therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia

    Outcome measured: Amyloid pathology and neuritic damage in a human-microglia xenograft mouse model given lecanemab, Fc-silenced lecanemab, or lecanemab with microglia depleted

    Direction is for lecanemab in mice: it significantly reduced amyloid pathology and neuritic damage, an effect absent with Fc-silenced antibody or without microglia despite intact plaque binding. Mouse work with no human outcome.

24. No direction reported None 2025

    Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer's disease

    Outcome measured: Microglial transcriptional states associated with amyloid clearance in post-mortem brain after active (AN1792) or passive (lecanemab) immunisation

    A mechanistic tissue study describing which microglial states accompany amyloid removal (TREM2 and APOE upregulation correlating with antibody response and clearance; complement signalling contributing). It estimates no effect of immunisation on a clinical outcome.

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