{"product_id":"simplified-blood-tests-accurately-confirm-alzheimers-brain-changes-before-starting-new-treatments","title":"Simplified Blood Tests Accurately Confirm Alzheimer's Brain Changes Before Starting New Treatments","description":"\u003cp\u003eTwo blood tests, when used together, can confirm whether a patient has the brain amyloid buildup that makes them eligible for new Alzheimer's disease-modifying therapies. In a study of nearly 400 Australians, the combination of phosphorylated tau 217 (p-tau217) and the amyloid beta 42\/40 (Aβ42\/40) ratio achieved over 90% accuracy in detecting amyloid positivity on brain scans. The test performed equally well in a group designed to mimic real-world patients who would seek treatment, with a sensitivity of 99% and specificity of 87%. These results suggest that a simple blood draw could replace more invasive cerebrospinal fluid tests when screening patients for drugs like lecanemab and donanemab.\u003c\/p\u003e\n\n\u003ch1\u003eSimplified Blood Tests Accurately Confirm Alzheimer's Brain Changes Before Starting New Treatments\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eBackground: Why These Blood Tests Matter\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eStudy Methods: How the Research Was Conducted\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#participants\"\u003eStudy Participants: Two Distinct Groups\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#bridging\"\u003eBridging Results Across Test Batches\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#biomarker-levels\"\u003eBlood Biomarker Levels Between Amyloid Positive and Negative Groups\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#correlations\"\u003eCorrelations Between Blood Markers and Brain Scan Amyloid Levels\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#predictive-performance\"\u003ePredictive Performance: How Well the Tests Detect Amyloid Positivity\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#clinical-implications\"\u003eClinical Implications: What This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations: What This Study Couldn't Prove\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations: What Patients Should Know\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn a study of 397 Australians, combining p-tau217 and Aβ42\/40 ratio blood tests detected brain amyloid with over 90% accuracy.\u003c\/li\u003e\n\u003cli\u003eAmong patients like those eligible for new Alzheimer's drugs, sensitivity was 99% and specificity was 87%.\u003c\/li\u003e\n\u003cli\u003eThe blood test met consensus criteria to replace cerebrospinal fluid or PET confirmation for most patients starting lecanemab or donanemab.\u003c\/li\u003e\n\u003cli\u003eAbout 10–15% of results fall in an intermediate gray zone, requiring PET or spinal fluid to decide treatment.\u003c\/li\u003e\n\u003cli\u003eTest results were highly reproducible, but participants were mostly White; broader ethnic applicability remains uncertain.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why These Blood Tests Matter\u003c\/h2\u003e\n\u003cp\u003eNew disease-modifying therapies (DMTs) for Alzheimer's disease (AD) — specifically lecanemab (marketed as Leqembi) and donanemab (marketed as Kisunla) — are now approved in several countries. These drugs work by removing amyloid beta (Aβ) plaques from the brain. To get these treatments, a patient must first show evidence of brain amyloid buildup, called \"Aβ positivity.\"\u003c\/p\u003e\n\u003cp\u003eCurrently, confirming Aβ positivity requires either a positron emission tomography (PET) brain scan or a lumbar puncture to collect cerebrospinal fluid (CSF). Both are expensive, time-consuming, and sometimes uncomfortable. Blood-based biomarkers (BBMs) — simple blood tests that measure proteins related to Alzheimer's — have advanced rapidly. However, doctors have lacked clear guidance on which blood test is good enough to confirm Aβ positivity before prescribing a DMT.\u003c\/p\u003e\n\u003cp\u003eIn 2023, a consensus statement defined the standards. A blood test can serve as a \u003cem\u003econfirmatory test\u003c\/em\u003e if it matches the performance of CSF biomarkers: at least 90% sensitivity (correctly identifying who has amyloid) and 90% specificity (correctly identifying who doesn't). If the test is not quite that good, it might still work as a \u003cem\u003etriaging test\u003c\/em\u003e — ruling out people who are unlikely to have amyloid — but then those who remain would still need a confirmatory PET scan or CSF test.\u003c\/p\u003e\n\u003cp\u003eThe current study aimed to see whether two plasma markers — p-tau217 and the Aβ42\/40 ratio, measured with a commercially available Fujirebio Lumipulse test — could meet the confirmatory test standard. The research team also wanted to define specific cut-off values that doctors could use in routine practice.\u003c\/p\u003e\n\u003ch2 id=\"methods\"\u003eStudy Methods: How the Research Was Conducted\u003c\/h2\u003e\n\u003ch3\u003eBlood sample collection\u003c\/h3\u003e\n\u003cp\u003eBlood was drawn from participants between 7:30 and 10:30 a.m. after an overnight fast. Samples were collected into tubes containing a substance to prevent platelet activation, then centrifuged to separate plasma. Plasma was frozen and stored in liquid nitrogen. Samples were later shipped on dry ice to Labcorp-Monogram Biosciences in South San Francisco, USA, for analysis.\u003c\/p\u003e\n\u003cp\u003eSamples were analyzed on a single Fujirebio Lumipulse G1200 instrument. The assays measured p-tau217, Aβ42, and Aβ40. The laboratory validated the tests according to official clinical standards (CAP-CLIA guidelines). Inter-assay precision was excellent — the coefficient of variation (a measure of result variability) was below 20%, and control accuracy was within 20% of expected values. The ADCC cohort was tested using one set of reagent lots (Aβ42 lot #3303, Aβ40 lot #3033, p-tau217 lot #4049). The ITTC cohort was tested about 12 months later using a different lot (Aβ1-42 lot #T6B5081, Aβ1-40 lot #T4B5112, p-tau217 lot #D4C5066).\u003c\/p\u003e\n\u003ch3\u003ePET imaging and amyloid classification\u003c\/h3\u003e\n\u003cp\u003eAll PET scans were performed within 12 months of the blood draw. Four different PET tracers were used: \u003csup\u003e11\u003c\/sup\u003eC-Pitttsburgh compound B (PiB), \u003csup\u003e18\u003c\/sup\u003eF-NAV4694 (NAV), \u003csup\u003e18\u003c\/sup\u003eF-flutemetamol (FLUTE), or \u003csup\u003e18\u003c\/sup\u003eF-florbetapir (FBP). Scan data were standardized to the Centiloid (CL) scale, a common measurement unit for brain amyloid.\u003c\/p\u003e\n\u003cp\u003eIn the ADCC (Alzheimer's disease continuum cohort), participants were classified as Aβ PET negative if their CL was below 15 and Aβ PET positive if their CL was 25 or higher. This allowed comparisons across the disease continuum. In the ITTC (intention-to-treat cohort), positivity was set at CL ≥25, consistent with the cognitively impaired population.\u003c\/p\u003e\n\u003ch3\u003eStatistical analysis\u003c\/h3\u003e\n\u003cp\u003eResearchers used receiver operating characteristic (ROC) curves to calculate area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Cut-offs were derived using two methods: the Youden index (maximizing sensitivity plus specificity) and dual cut-offs (setting both sensitivity and specificity to at least 95%, which leaves a \"gray zone\" between them).\u003c\/p\u003e\n\u003cp\u003eThey also compared models that added demographic factors — age, sex, apolipoprotein E (APOE) ε4 status, and PET tracer type — to the blood biomarkers. A technique called least absolute shrinkage and selection operator (LASSO) was used for multivariate selection of the best combination of markers.\u003c\/p\u003e\n\u003ch2 id=\"participants\"\u003eStudy Participants: Two Distinct Groups\u003c\/h2\u003e\n\u003cp\u003eThe study used samples from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) Study of Ageing. Two separate sub-cohorts were selected, with no participant included in both groups.\u003c\/p\u003e\n\u003ch3\u003eAD continuum cohort (ADCC)\u003c\/h3\u003e\n\u003cp\u003eThis cohort was designed to assess plasma biomarker levels across the entire Alzheimer's disease spectrum. It included:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e75 cognitively unimpaired, Aβ PET negative participants (CUAβ–); roughly 50% had subjective memory complaints\u003c\/li\u003e\n  \u003cli\u003e48 cognitively unimpaired, Aβ PET positive participants (CUAβ+); 66% had subjective memory complaints\u003c\/li\u003e\n  \u003cli\u003e26 participants with mild cognitive impairment (MCI) who were Aβ PET positive (MCI Aβ+)\u003c\/li\u003e\n  \u003cli\u003e48 participants with AD dementia who were Aβ PET positive (AD Aβ+)\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eTotal sample: 197 participants. Of these, 62% were Aβ PET positive. Among the cognitively unimpaired group, 39% had preclinical AD (Aβ+), while 61% were Aβ–. There were no significant differences in age or sex between the Aβ groups, but all other clinical parameters differed significantly (p\u0026lt;0.0001). The mean age was 75.1 years (standard deviation 7.3). The mean Centiloid value was 56.7 in the overall sample, −0.5 in Aβ– participants, and 91.9 in Aβ+ participants.\u003c\/p\u003e\n\u003ch3\u003eIntention-to-treat cohort (ITTC)\u003c\/h3\u003e\n\u003cp\u003eThis cohort was designed to mimic the patient population that would actually present in primary\/secondary care and meet the inclusion criteria for a DMT. Eligibility for lecanemab or donanemab in clinical trials required a Clinical Dementia Rating of 0.5–1 and a Mini-Mental State Examination (MMSE) score of 22–28. (Note: approval criteria vary by country — for example, in the US any number of APOE ε4 alleles is allowed, while in Australia and the EU only 0 or 1 copy is allowed.)\u003c\/p\u003e\n\u003cp\u003eThe ITTC included:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e65 MCI Aβ+ participants\u003c\/li\u003e\n  \u003cli\u003e61 AD dementia Aβ+ participants\u003c\/li\u003e\n  \u003cli\u003e59 MCI Aβ– participants\u003c\/li\u003e\n  \u003cli\u003e15 AD dementia Aβ– participants\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eTotal sample: 200 participants. Of these, 62.5% had MCI and 37.5% had mild AD. In the MCI group, 52% were Aβ+; in the AD group, 80% were Aβ+. Overall, 63% were Aβ PET positive. No significant age or sex differences existed between Aβ groups, but other clinical parameters differed significantly (p\u0026lt;0.0001). Mean age was 73.6 years (SD 8.4). Mean Centiloid was 64 overall, −0.6 in Aβ–, and 101.9 in Aβ+.\u003c\/p\u003e\n\u003ch2 id=\"bridging\"\u003eBridging Results Across Test Batches\u003c\/h2\u003e\n\u003cp\u003eBecause the two cohorts were measured about 12 months apart, the researchers ran a bridging study to make sure results from both batches could be compared fairly. They re-ran 40 samples from the ADCC cohort (10 from each of the four diagnostic groups: CUAβ–, CUAβ+, MCI Aβ+, AD Aβ+) at the same time as the ITTC samples.\u003c\/p\u003e\n\u003cp\u003eBland–Altman analysis showed small systematic differences between runs. The bias ranged from about a 0.7% decrease for Aβ40 to about a 7% increase for Aβ42 and p-tau217 in the ITTC compared to ADCC. The standard deviation of the differences was small — less than 1 standard deviation of the original ADCC measurements for each biomarker (Aβ40: 0.26 SD, Aβ42: 0.19 SD, p-tau217: 0.12 SD). Concordance correlations for all three assays ranged from 0.93 to 0.99.\u003c\/p\u003e\n\u003cp\u003eBecause the variability between the two batches was consistent, all ITTC data were transformed using Deming regression equations so that the results from both cohorts were on the same scale. This ensures that the cut-off values derived from one cohort can be applied to the other.\u003c\/p\u003e\n\u003ch2 id=\"biomarker-levels\"\u003eBlood Biomarker Levels Between Amyloid Positive and Negative Groups\u003c\/h2\u003e\n\u003cp\u003eAll four biomarkers — Aβ42, p-tau217, Aβ42\/40, and the p-tau217\/Aβ42 ratio — were significantly different in Aβ PET+ groups compared to Aβ PET– groups in both cohorts. The differences remained significant even after adjusting for age, sex, APOE ε4 status, and PET tracer (p\u0026lt;0.001 in all cases).\u003c\/p\u003e\n\u003cp\u003eThe strongest effect was seen for the p-tau217\/Aβ42 ratio. In the ADCC, the mean ratio was 0.006 in Aβ– and 0.026 in Aβ+ (Cohen's D = 2.43, p=1.25E-37 unadjusted; p=1.67E-09 adjusted). In the ITTC, the ratio was 0.006 in Aβ– and 0.030 in Aβ+ (Cohen's D = 2.69, p=2.13E-40 unadjusted; p=1.03E-10 adjusted). Cohen's D is a measure of effect size; values above 0.8 are considered large, and here the values were extremely large.\u003c\/p\u003e\n\u003cp\u003eIndividual biomarker means were also reported (values in pg\/mL, though the paper doesn't specify units explicitly):\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eAβ42 in ADCC: 27.969 (Aβ–) vs 23.484 (Aβ+), Cohen's D=0.928\u003c\/li\u003e\n  \u003cli\u003ep-tau217 in ADCC: 0.154 (Aβ–) vs 0.596 (Aβ+), D=2.17\u003c\/li\u003e\n  \u003cli\u003eAβ42\/40 in ADCC: 0.092 vs 0.076, D=1.81\u003c\/li\u003e\n  \u003cli\u003eAβ42 in ITTC: 28.212 (Aβ–) vs 22.853 (Aβ+), D=1.14\u003c\/li\u003e\n  \u003cli\u003ep-tau217 in ITTC: 0.168 vs 0.663, D=2.36\u003c\/li\u003e\n  \u003cli\u003eAβ42\/40 in ITTC: 0.090 vs 0.074, D=2.41\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThe Aβ42\/40 ratio showed significantly larger effect sizes compared to Aβ42 alone in both cohorts (ADCC: p=0.0001; ITTC: p\u0026lt;0.0001). However, the p-tau217\/Aβ42 ratio did not significantly outperform p-tau217 alone (ADCC: p=0.318; ITTC: p=0.223).\u003c\/p\u003e\n\u003ch2 id=\"correlations\"\u003eCorrelations Between Blood Markers and Brain Scan Amyloid Levels\u003c\/h2\u003e\n\u003cp\u003eThe study also examined how well the blood markers tracked with the actual amount of brain amyloid measured on the Centiloid scale.\u003c\/p\u003e\n\u003cp\u003eAβ42\/40 showed a moderate inverse correlation with CL — meaning lower blood ratios were associated with higher brain amyloid. The correlation coefficient (Rho) was −0.507 in the ADCC and −0.602 in the ITTC. The ratio had less variance than Aβ42 alone, making it a more stable indicator.\u003c\/p\u003e\n\u003cp\u003eUsing Aβ42\/40 to classify Aβ PET status, only 4% of participants in the ADCC and 2% in the ITTC were false negatives (blood test said negative but scan was positive). False positives (blood positive, scan negative) were 8% in ADCC and 6% in ITTC.\u003c\/p\u003e\n\u003cp\u003ep-tau217 showed strong positive correlations with CL: Rho = 0.732 (ADCC) and 0.723 (ITTC). The p-tau217\/Aβ42 ratio correlated even better: Rho = 0.751 (ADCC) and 0.753 (ITTC). Compared to p-tau217 alone, using the p-tau217\/Aβ42 ratio reduced false positives from 7% to 4% in the ADCC, with limited change in the ITTC (4% to 5%). False negatives decreased from 4% to 0% in the ITTC.\u003c\/p\u003e\n\u003ch2 id=\"predictive-performance\"\u003ePredictive Performance: How Well the Tests Detect Amyloid Positivity\u003c\/h2\u003e\n\u003cp\u003eThe central question was whether the blood tests could match the performance of CSF biomarkers (at least 90% sensitivity and specificity). The answer was yes — particularly when the two markers were combined.\u003c\/p\u003e\n\u003ch3\u003eADCC results\u003c\/h3\u003e\n\u003cp\u003eIn the ADCC, individual biomarker AUCs for predicting Aβ PET status were strongest for p-tau217 and the p-tau217\/Aβ42 ratio:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003ep-tau217\/Aβ42 ratio: AUC = 0.961\u003c\/li\u003e\n  \u003cli\u003ep-tau217 alone: AUC = 0.941\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eUsing the p-tau217\/Aβ42 ratio with a cut-off derived from the Youden index, the sensitivity was 93%, specificity 92%, and overall accuracy 93%.\u003c\/p\u003e\n\u003cp\u003eAdding age, sex, and APOE ε4 status to the biomarkers increased the AUC for Aβ42 and the Aβ42\/40 ratio only. It did not improve the performance of p-tau217 or the p-tau217\/Aβ42 ratio.\u003c\/p\u003e\n\u003cp\u003eIn a pre-clinical AD subgroup (cognitively unimpaired participants only), the Aβ42\/40 ratio had a higher AUC (0.906) compared to the complete ADCC (0.893), but this difference was not statistically significant (p\u0026gt;0.05). Adding demographic factors did not improve AUC for any biomarker in this subgroup.\u003c\/p\u003e\n\u003ch3\u003eITTC results\u003c\/h3\u003e\n\u003cp\u003eWhen the same cut-offs derived from the ADCC were applied to the ITTC, the AUC remained virtually identical: 0.959 for the p-tau217\/Aβ42 ratio. However, the test characteristics differed in this real-world-like population:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eSensitivity increased to 99%\u003c\/li\u003e\n  \u003cli\u003eSpecificity decreased to 87%\u003c\/li\u003e\n  \u003cli\u003eOverall accuracy increased to 95%\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eIn the ITTC, the composite score (a linear combination of APOE ε4 + age + Aβ42 + p-tau217 + Aβ42\/40 + p-tau217\/Aβ42), the linear combination of Aβ42\/40 with p-tau217 plus age, sex, and APOE ε4, and the p-tau217\/Aβ42 ratio alone were all significantly better (nominally, unadjusted) at predicting Aβ PET status compared to p-tau217 alone (p=0.013, p=0.010, and p=0.009, respectively).\u003c\/p\u003e\n\u003ch3\u003eDual cut-offs and the intermediate zone\u003c\/h3\u003e\n\u003cp\u003eThe authors also tested a dual cut-off approach, aiming for 95% sensitivity and 95% specificity. This creates an intermediate \"gray zone\" where results are not conclusive. In both cohorts, the intermediate zone contained only 10% to 15% of participants. For those in the gray zone, a confirmatory PET scan or CSF test would still be needed.\u003c\/p\u003e\n\u003cp\u003eThis dual cut-off strategy resulted in 93% overall accuracy. Critically, less than 15–20% of patients fall into the ambiguous intermediate zone, which is the recommended maximum. This means the test can confidently classify the vast majority of people.\u003c\/p\u003e\n\u003ch2 id=\"clinical-implications\"\u003eClinical Implications: What This Means for Patients\u003c\/h2\u003e\n\u003cp\u003eFor a patient with memory complaints who is being evaluated for lecanemab or donanemab, this study suggests that a single blood test can replace the need for a lumbar puncture or PET scan in most cases.\u003c\/p\u003e\n\u003cp\u003eIf the blood test result falls clearly below the low cut-off, the patient is almost certainly Aβ negative and should not be given a DMT. If the result is clearly above the high cut-off, the patient is almost certainly Aβ positive and can proceed to treatment — after confirming eligibility based on other clinical factors (such as MMSE score and APOE status).\u003c\/p\u003e\n\u003cp\u003eThe sensitivity of 99% in the ITTC group is reassuring: fewer than 1 in 100 patients with true brain amyloid would be missed. The specificity of 87% means that about 13 in 100 people without amyloid might be told they are positive; however, the study authors note that most of these false positives would fall in an intermediate range, prompting further testing. Using the dual cut-offs, the number of people needing additional confirmation is kept to just 10–15%.\u003c\/p\u003e\n\u003cp\u003eThe study specifically validated these results in a cohort that matches the real population who would seek DMTs: people with MCI or mild AD, with MMSE scores of 22–28. This is exactly the group for which the drugs are approved.\u003c\/p\u003e\n\u003cp\u003eAnother practical advantage: the tests use the same Lumipulse platform already available in many clinical labs. The assay performance was rigorously validated, with inter-assay precision of 1.6% to 2.2% for high and low controls, far exceeding the required standards.\u003c\/p\u003e\n\u003ch2 id=\"limitations\"\u003eLimitations: What This Study Couldn't Prove\u003c\/h2\u003e\n\u003cp\u003eThis study has several limitations that patients and clinicians should consider.\u003c\/p\u003e\n\u003cp\u003eFirst, the participants were all from the AIBL study in Australia, a research cohort that is predominantly White and of European ancestry. The authors note that there is insufficient evidence in under-represented ethnic populations, which can affect generalizability.\u003c\/p\u003e\n\u003cp\u003eSecond, the study used PET imaging as the reference standard. PET scans are imperfect at classifying borderline amyloid levels. Participants with CL values between 15 and 25 were deliberately excluded from the ADCC analysis, which may inflate the apparent test performance. The cutoff of ≥25 CL to define Aβ positivity also differs from some other studies that use ≥12 or ≥30.\u003c\/p\u003e\n\u003cp\u003eThird, clinical classification within AIBL was based solely on neuropsychological test scores and a clinical panel decision, without using biomarker data. This is actually a strength for assessing the blood tests independently, but it also means the diagnostic categories rely on standard clinical judgment rather than a gold standard pathology.\u003c\/p\u003e\n\u003cp\u003eFourth, the bridging study between reagent lots was performed with a small sample (40 samples) that included only 10 from each diagnostic group. While the concordance correlations were high (0.93–0.99), some variability remains.\u003c\/p\u003e\n\u003cp\u003eFifth, the study does not tell us whether these blood tests can monitor a patient's response to DMT over time. The authors note this as a future direction: \"When BBM data post-DMT become available, the question of whether these cut-offs can be used at a point where sufficient brain Aβ has been removed and treatment can be stopped needs to be addressed.\"\u003c\/p\u003e\n\u003cp\u003eFinally, the statistical comparisons were generally not corrected for multiple testing. The authors acknowledge that some p-values between 0.002 and 0.05 should be considered \"nominally significant\" rather than definitive.\u003c\/p\u003e\n\u003ch2 id=\"recommendations\"\u003eRecommendations: What Patients Should Know\u003c\/h2\u003e\n\u003cp\u003eIf you or a loved one is being evaluated for a disease-modifying Alzheimer's therapy, here are the key takeaways:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about blood-based biomarker testing.\u003c\/strong\u003e The combination of p-tau217 and the Aβ42\/40 ratio, measured with Lumipulse, meets the international consensus criteria for a confirmatory test in populations similar to DMT candidates. This means it can replace CSF testing or PET in most cases.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eUnderstand your numbers.\u003c\/strong\u003e Your doctor will receive a value for the p-tau217\/Aβ42 ratio. Low values (in the range of \u0026lt;0.006) are consistent with no brain amyloid; high values (above the upper cut-off, which the paper does not explicitly state but corresponds to roughly \u0026gt;0.03 on the transformed scale) indicate likely amyloid positivity. Many results will fall clearly on one side.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKnow that a gray zone exists.\u003c\/strong\u003e In 10–15% of cases, results are intermediate. If you fall in this zone, your doctor will recommend a PET scan or spinal fluid test to make the final decision. This is a small price to pay for avoiding unnecessary treatment.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eThe test is highly sensitive but not perfect.\u003c\/strong\u003e A negative result (below the low cut-off) means you have a less than 1% chance of having significant brain amyloid, based on the ITTC sensitivity of 99%. A positive result means about an 87% chance you have amyloid — confirmed with a PET scan if needed.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDemographics don't change the story.\u003c\/strong\u003e Adding age, sex, and APOE ε4 did not improve the predictive power of the p-tau217\/Aβ42 ratio. So you don't need complex models to interpret your result.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTests are reliable.\u003c\/strong\u003e The Lumipulse platform used in this study showed very low variability between runs (coefficients of variation from 0.2% to 2.2%), meaning results are reproducible.\u003c\/li\u003e\n\u003c\/ol\u003e\n\u003cp\u003eAs always, talk to your healthcare provider about which tests are covered by your insurance and what they mean in your specific situation. The evidence is strong, but this is a rapidly evolving field — new cut-offs and recommendations may appear as more data emerge.\u003c\/p\u003e\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat blood test can confirm brain amyloid buildup before starting Alzheimer's treatment?\u003c\/h3\u003e\n\u003cp\u003eA simple blood test measuring two markers – p-tau217 and the amyloid beta 42\/40 ratio – can confirm brain amyloid buildup. In a study of nearly 400 Australians, this combination matched the accuracy of spinal fluid tests. If you're being evaluated for lecanemab or donanemab, ask your doctor if this blood test is available.\u003c\/p\u003e\n\u003ch3\u003eCan this blood test replace the lumbar puncture or PET scan before I receive Alzheimer's treatment?\u003c\/h3\u003e\n\u003cp\u003eYes, for most people. The combination test meets international criteria as a confirmatory test, so a spinal tap or PET scan is often unnecessary. However, in about 10–15% of results, the test falls into an intermediate gray zone, and then a PET scan or spinal fluid test is still needed to make the final decision.\u003c\/p\u003e\n\u003ch3\u003eWhat happens if my blood test result is in the gray zone?\u003c\/h3\u003e\n\u003cp\u003eIf your result is uncertain – not clearly positive or negative – doctors will recommend a PET brain scan or a lumbar puncture to confirm whether you have brain amyloid. Only about 10–15% of people get an inconclusive result, so most patients can avoid these extra procedures.\u003c\/p\u003e\n\u003ch3\u003eWhat does a positive or negative result mean for getting lecanemab or donanemab?\u003c\/h3\u003e\n\u003cp\u003eA clearly negative result means you have less than a 1% chance of significant brain amyloid, so these drugs are unlikely to help. A clearly positive result means about 87% chance you have amyloid, and you may proceed with treatment if other eligibility criteria are met. Your doctor will interpret the exact number.\u003c\/p\u003e\n\u003ch3\u003eDo these blood test results apply to people of all ethnic backgrounds?\u003c\/h3\u003e\n\u003cp\u003eThe study participants were from an Australian research cohort, mostly of European ancestry. Researchers noted insufficient evidence in under-represented ethnic populations, which may affect generalizability. If you are from a different ethnic background, discuss with your doctor whether these test thresholds are appropriate for you.\u003c\/p\u003e\n\u003ch3\u003eI had a p-tau217 and Aβ42\/40 blood test that says I have brain amyloid. Should I get a second opinion before starting lecanemab or donanemab?\u003c\/h3\u003e\n\u003cp\u003eBefore starting lecanemab or donanemab, a second opinion is worth seeking if your doctor's plan rests on a blood test alone. The combination of p-tau217 and the Aβ42\/40 ratio has been shown to be a confirmatory test with over 90% accuracy against brain scans. In the population matching treatment candidates, sensitivity was 99% and specificity 87%. About 10–15% of results fall in an intermediate gray zone that still needs PET or spinal fluid testing. A second opinion can check whether your result is conclusive, whether additional confirmation is appropriate, and whether eligibility criteria such as MMSE score and APOE status are met. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\u003cp\u003eThis patient-friendly article is based on peer-reviewed research.\u003c\/p\u003e\n\u003cp\u003eOriginal article title: \"Combining Lumipulse p-tau217 and Aβ42\/40 as confirmatory tests for Aβ positivity prior to disease-modifying therapy\"\u003c\/p\u003e\n\u003cp\u003eAuthors: James D. Doecke, Ahmed Chenna, Mintzu Lo, Youssouf Badal, Brandon Yee, Robert Martone, Christos Petropoulos, Christopher J. Fowler, Simon Laws, Stephanie R. Rainey-Smith, Ralph N. Martins, Christopher C. Rowe, Colin L. Masters, John Winslow\u003c\/p\u003e\n\u003cp\u003ePublication: \u003cem\u003eAlzheimer's \u0026amp; Dementia\u003c\/em\u003e, 2025;21:e70707. DOI: 10.1002\/alz.70707\u003c\/p\u003e\n\u003cp\u003ePublished under the Creative Commons Attribution-NonCommercial-NoDerivs License, © 2025 The Author(s).\u003c\/p\u003e\n\u003cp\u003eThis summary aims to make the research accessible while preserving all key findings, numbers, and caveats. It does not replace medical advice. Always consult a qualified clinician.\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47560936849564,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"url":"https:\/\/diagnosticdetectives.com\/ar\/products\/simplified-blood-tests-accurately-confirm-alzheimers-brain-changes-before-starting-new-treatments","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}