scholarly journals Alzheimer’s cerebrospinal biomarkers from Lumipulse fully automated immunoassay: concordance with amyloid-beta PET and manual immunoassay in Koreans

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sohee Moon ◽  
Sujin Kim ◽  
Sakulrat Mankhong ◽  
Seong Hye Choi ◽  
Manu Vandijck ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Clinical Utility ◽  
Brain Aging ◽  
Csf Biomarkers ◽  
Rapid Progression ◽  
Amyloid Pet ◽  
Positron Emission ◽  
Csf Biomarker ◽  
Automated Immunoassay ◽  
T Tau

Abstract Background Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability in diverse ethnic groups are necessary for their use in clinics and clinical trials. With lack of cutoffs from fully automated immunoassay platforms in diverse races, the aim of this study is to evaluate the clinical utility of CSF AD biomarkers from the Lumipulse fully automated immunoassay based on β-amyloid (Aβ) positron emission tomography (PET) status comparing with these from two manual immunoassays, in Koreans. Methods Among 331 Korean participants enrolled from a prospective, 3-year longitudinal observational study of the validation cohort of Korean Brain Aging Study for the Early Diagnosis and Prediction of AD, 139 (29 CN, 58 SCD, 29 MCI, and 23 AD) provided CSF and 271 underwent baseline amyloid PET (n = 128 with overlapping CSF and Aβ-PET, and 143 without CSFs). Three annual cognitive and neuropsychiatric function tests were conducted. Aβ42, Aβ40, total-tau, and phosphorylated-tau181 were measured by Lumipulse fully automated immunoassay and two manual immunoassays (INNO-BIA AlzBio3, INNOTEST). Clinical utility of CSF biomarker cutoffs, based on 128 participants with Aβ-PET, was evaluated. Results Cognitive and neuropsychological scores differed significantly among the groups, with descending performance among CN>SCD>MCI>AD. Biomarker levels among immunoassays were strongly intercorrelated. We determined the Aβ-PET status in a subgroup without CSF (n = 143), and then when we applied CSF biomarker cutoffs determined based on the Aβ-PET status, the CSF biomarkers (cutoffs of 642.1 pg/mL for Aβ42, 0.060 for Aβ42/Aβ40, 0.315 for t-tau/Aβ42, and 0.051 for p-tau/Aβ42, respectively) showed good agreement with Aβ-PET (overall AUC ranges of 0.840–0.898). Use of the Aβ-PET-based CSF cutoffs showed excellent diagnostic discrimination between AD and CN (Aβ42, Aβ42/Aβ40, t-tau/Aβ42, and p-tau/Aβ42) with overall AUC ranges of 0.876–0.952. During follow-up, participants with AD-like CSF signature determined by Aβ-PET-based cutoffs from Lumipulse showed rapid progression of cognitive decline in 139 subjects, after adjustment for potential confounders, compared with those with a normal CSF signature. Conclusion CSF AD biomarkers measured by different immunoassay platforms show strong intercorrelated agreement with Aβ-PET in Koreans. The Korean-specific Aβ-PET-based CSF biomarker cutoffs measured by the Lumipulse assay strongly predicts progression of cognitive decline. The clinical utility of CSF biomarkers from fully-automated immunoassay platforms should be evaluated in larger, more diverse cohorts.

scholarly journals Alzheimer’s Cerebrospinal Biomarkers from Lumipulse Fully Automated Immunoassay: Concordance with Amyloid-Beta PET and Manual Immunoassay in Koreans

2020 ◽  
Author(s):  
Sohee Moon ◽  
Sujin Kim ◽  
Sakulrat Mankhong ◽  
Seong Hye Choi ◽  
Manu Vandijck ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Cognitive Decline ◽  
Clinical Utility ◽  
Brain Aging ◽  
Subjective Cognitive Decline ◽  
Csf Biomarkers ◽  
Rapid Progression ◽  
Amyloid Pet ◽  
Csf Biomarker ◽  
Automated Immunoassay

Abstract Background: Universal Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability could improve diagnostic accuracy and help predict disease progression. To determine the diagnostic cutoffs of CSF AD biomarkers measured with three immunoassay platforms, including fully automated Lumipulse based on b-amyloid (Ab) positron emission tomography (PET) status, to determine diagnostic utility and clinical predictability.Methods: Three hundred thirty-one Korean participants were enrolled from a prospective, 3-year longitudinal observational study of the validation cohort of Korean Brain Aging Study for the Early Diagnosis and Prediction of AD: 71 cognitively normal (CN), 99 with subjective cognitive decline (SCD), 89 with mild cognitive impairment (MCI), and 72 with AD. Among these 331 participants, 139 (29, 58, 29, and 23 from each group, respectively) provided CSF and 271 underwent baseline amyloid PET. Three annual cognitive and neuropsychiatric function tests were conducted. Ab42, Ab40, total-tau and phosphorylated-tau181 were measured by Lumipulse fully automated immunoassay and two manual immunoassays (INNO-BIA AlzBio3, INNOTEST). Clinical utility of CSF biomarker cutoffs, based on 128 participants with Ab-PET, were evaluated.Results: Cognitive and neuropsychological scores differed significantly among the groups, with descending performance among CN > SCD > MCI > AD. Biomarker levels among immunoassays were strongly intercorrelated, and using the cutoffs for Ab-PET status with maximal AD diagnostic accuracy (n = 215), the levels showed excellent agreement with Ab-PET. Use of Ab-PET-based cutoffs for CSF biomarkers showed excellent diagnostic discrimination between AD and CN (Ab42, Ab42/Ab40, t-tau/Ab42 and p-tau/Ab42) with overall AUC ranges to discriminate AD and CN (0.876–0.952). During follow-up, participants with AD-like CSF signature determined by Ab-PET-based cutoffs from Lumipulse showed rapid progression of clinical scores, after adjustment for potential confounders, compared with those with a normal CSF signature.Conclusion: CSF AD biomarkers measured by different immunoassay platforms show strong intercorrelated agreement with Ab-PET. Ab-PET-based CSF biomarker cutoffs measured by immunoassays, including the Lumipulse, strongly predict progression of cognitive decline. The clinical utility of CSF biomarkers from fully automated immunoassay platforms should be evaluated in larger, more diverse cohorts.

scholarly journals Clinical utility of Cerebrospinal Fluid Biomarkers for the Diagnosis of Alzheimer’s Disease in Korea

2020 ◽  
Author(s):  
Jongmin Lee ◽  
Hyemin Jang ◽  
Sung Hoon Kang ◽  
Jaeho Kim ◽  
Ji-Sun Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Clinical Utility ◽  
Medical Center ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Characteristic Analysis ◽  
Csf Biomarker ◽  
T Tau

Abstract Background Cerebrospinal fluid (CSF) biomarkers are increasingly used in clinical practice for the diagnosis of Alzheimer’s disease (AD). We aimed to 1) determine cutoff values of CSF biomarkers for AD, 2) investigate their clinical utility by estimating a concordance with amyloid positron emission tomography (PET), and 3) apply AT (amyloid/tau) classification based on CSF results. Methods We performed CSF analysis in 51 normal controls (NC), 23 amnestic mild cognitive impairment (aMCI) and 65 AD dementia (ADD) patients at the Samsung Medical Center in Korea. We tried to develop cutoff of CSF biomarkers for differentiating ADD from NC using receiver operating characteristic analysis. We also investigated a concordance between CSF and amyloid PET results and applied AT classification scheme based on CSF biomarker abnormalities to characterize our participants. Results CSF Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) significantly differ across the three groups. The area under curve for the differentiation between NC and ADD was highest in t-tau/Aβ42(0.994) followed by p-tau/Aβ42(0.963), Aβ42(0.960) and t-tau (0.918). The concordance rate between CSF Aβ42 and amyloid PET results was 92%. Finally, AT classification based on CSF biomarker abnormalities led to a majority of NC categorized into A-T-(72%), aMCI as A + T-(52%)/A + T+(30%), and AD as A + T+(56%)/A + T-(41%). Conclusion CSF biomarkers had high sensitivity and specificity in differentiating ADD from NC and were as accurate as amyloid PET. The AT group distribution was comparable to those of previous studies, which may serve to predict the prognosis more accurately than amyloid PET alone in the future.

scholarly journals Cognitive trajectories of patients with focal ß-amyloid deposition

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Si Eun Kim ◽  
Byungju Lee ◽  
Hyemin Jang ◽  
Juhee Chin ◽  
Ching Soong Khoo ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Neuropsychological Tests ◽  
Mixed Effects ◽  
Amnestic Mild Cognitive Impairment ◽  
Emission Tomography ◽  
Amyloid Pet ◽  
Cognitive Level ◽  
Visual Rating ◽  
Positron Emission ◽  
The Brain

Abstract Background The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition. Methods We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer’s disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1–9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group. Results Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7–9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1–3 or 4–6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex. Conclusions When predicting cognitive decline of patients with focal Aß deposition, the patients’ cognitive level, extent, and location of the focal involvement are important.

scholarly journals Association of midlife vascular risk and AD biomarkers with subsequent cognitive decline

Neurology ◽  
2020 ◽  
Vol 95 (23) ◽  
pp. e3093-e3103
Author(s):  
Corinne Pettigrew ◽  
Anja Soldan ◽  
Jiangxia Wang ◽  
Mei-Cheng Wang ◽  
Karissa Arthur ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Risk Score ◽  
Synergistic Effects ◽  
Vascular Risk Factor ◽  
Rate Of Change ◽  
Csf Biomarkers ◽  
Vascular Risk ◽  
Cognitively Normal ◽  
T Tau

ObjectiveTo determine whether vascular risk and Alzheimer disease (AD) biomarkers have independent or synergistic effects on cognitive decline and whether vascular risk is associated with the accumulation of AD pathology as measured by change in biomarkers over time.MethodsAt baseline, participants (n = 168) were cognitively normal and primarily middle-aged (mean 56.4 years, SD 10.9 years) and had both vascular risk factor status and proximal CSF biomarkers available. Baseline vascular risk was quantified with a composite vascular risk score reflecting the presence or absence of hypertension, hypercholesterolemia, diabetes, current smoking, and obesity. CSF biomarkers of β-amyloid (Aβ)1–42, total tau (t-tau), and phosphorylated tau (p-tau) were used to create dichotomous high and low AD biomarker groups (based on Aβ1–42 and tau). Linear mixed-effects models were used to examine change in a cognitive composite score (mean follow-up 13.9 years) and change in CSF biomarkers (mean follow-up 4.2 years).ResultsThere was no evidence of a synergistic relationship between the vascular risk score and CSF AD biomarkers and cognitive decline. Instead, the vascular risk score (estimate −0.022, 95% confidence interval [CI] −0.043 to −0.002, p = 0.03) and AD biomarkers (estimate −0.060, 95% CI −0.096 to −0.024, p = 0.001) were independently and additively associated with cognitive decline. In addition, the vascular risk score was unrelated to levels of or rate of change in CSF Aβ1–42, t-tau, or p-tau.ConclusionsThe results of this observational cohort study suggest that vascular risk and biomarkers of AD pathology, when measured in midlife, act along independent pathways and underscore the importance of accounting for multiple risk factors for identifying cognitively normal individuals at the greatest risk of cognitive decline.

scholarly journals A Review of Diagnostic Impact of Amyloid Positron Emission Tomography Imaging in Clinical Practice

2018 ◽  
Vol 46 (3-4) ◽  
pp. 154-167 ◽  
Author(s):  
Yejin Kim ◽  
Paul Rosenberg ◽  
Esther Oh
Keyword(s):  
Positron Emission Tomography ◽  
Clinical Practice ◽  
Pet Imaging ◽  
Clinical Utility ◽  
Patient Management ◽  
Emission Tomography ◽  
Amyloid Pet ◽  
Diagnostic Confidence ◽  
Positron Emission ◽  
Amyloid Pet Imaging

Background: Molecular imaging of brain amyloid for the diagnosis of Alzheimer’s disease (AD) using positron emission tomography (PET) has been approved for use in clinical practice by the Food and Drug Administration (FDA) since 2012. However, the clinical utility and diagnostic impact of amyloid PET imaging remain controversial. We conducted a review of the recent studies investigating clinical utility of amyloid PET imaging with focus on changes in diagnosis, diagnostic confidence, and patient management. Summary: A total of 16 studies were included in the final analysis. Overall rate of changes in diagnosis after amyloid PET ranged from 9 to 68% (pooled estimate of 31%, 95% CI 23–39%). All studies reported overall increase in diagnostic confidence or diagnostic certainty after amyloid PET. Changes in patient management ranged from 37 to 87%; the most common type of change in management reported was either the initiation or discontinuation of planned AD medications. Key Messages: Amyloid PET imaging led to moderate to significant changes in diagnosis, diagnostic confidence, and subsequent patient management. It may be most useful in patients with high level of diagnostic uncertainty even after the completing the standard workup.

scholarly journals Biomarker pattern of ARIA-E participants in phase 3 randomized clinical trials with bapineuzumab

Neurology ◽  
2018 ◽  
Vol 90 (10) ◽  
pp. e877-e886 ◽  
Author(s):  
Enchi Liu ◽  
Dai Wang ◽  
Reisa Sperling ◽  
Stephen Salloway ◽  
Nick C. Fox ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Hippocampal Volume ◽  
Volume Reduction ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Ventricular Enlargement ◽  
Lower Baseline ◽  
Biomarker Pattern ◽  
T Tau

ObjectiveTo evaluate whether amyloid-related imaging abnormalities with edema/effusion (ARIA-E) observed in bapineuzumab clinical trials was associated with specific biomarker patterns.MethodsBapineuzumab, an anti-β-amyloid monoclonal antibody, was evaluated in patients with mild to moderate Alzheimer disease. Amyloid PET imaging, CSF biomarkers, or volumetric MRI (vMRI) were assessed.ResultsA total of 1,512 participants underwent one or more biomarker assessments; 154 developed incident ARIA-E. No differences were observed at baseline between ARIA-E and non-ARIA-E participants in brain amyloid burden by PET, the majority of vMRI measures, or CSF biomarkers, with the exception of lower baseline CSF Aβ42 in APOE ε4 noncarrier ARIA-E vs non-ARIA-E groups (bapineuzumab non-ARIA-E p = 0.027; placebo non-ARIA-E p = 0.012). At week 71, bapineuzumab-treated participants with ARIA-E vs non-ARIA-E showed greater reduction in brain amyloid PET, greater reductions in CSF phosphorylated tau (p-tau) (all comparisons p < 0.01), and total tau (t-tau) (all comparisons p < 0.025), and greater hippocampal volume reduction and ventricular enlargement (all p < 0.05). Greater reduction in CSF Aβ40 concentrations was observed for ARIA-E versus both non-ARIA-E groups (bapineuzumab/placebo non-ARIA-E p = 0.015/0.049). No group differences were observed at week 71 for changes in whole brain volume or CSF Aβ42.ConclusionsBaseline biomarkers largely do not predict risk for developing ARIA-E. ARIA-E was associated with significant longitudinal changes in several biomarkers, with larger reductions in amyloid PET and CSF p-tau and t-tau concentrations, and paradoxically greater hippocampal volume reduction and ventricular enlargement, suggesting that ARIA-E in bapineuzumab-treated cases may be related to increased Aβ efflux from the brain and affecting downstream pathogenic processes.

scholarly journals Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer’s disease

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz2387 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Emelie Andersson ◽  
Shorena Janelidze ◽  
Rik Ossenkoppele ◽  
Philip Insel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Phosphorylated Tau ◽  
Positron Emission ◽  
Aβ Aggregation ◽  
Tau Pet ◽  
5Xfad Mice ◽  
Tau Aggregation ◽  
T Tau

The links between β-amyloid (Aβ) and tau in Alzheimer’s disease are unclear. Cognitively unimpaired persons with signs of Aβ pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without Aβ pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when Aβ aggregation started. These results show that Aβ pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.

scholarly journals Agreement between 18F-Florbetapir PET imaging and cerebrospinal fluid Aβ1-42, Aβ1-40, tTau and pTau measured on the LUMIPULSE G fully automated platform

2018 ◽  
Author(s):  
Daniel Alcolea ◽  
Jordi Pegueroles ◽  
Laia Muñoz ◽  
Valle Camacho ◽  
Diego López-Mora ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Diagnostic Agreement ◽  
Amyloid Pathology ◽  
Automated Quantification ◽  
Automated Platform ◽  
Automated Immunoassay ◽  
Technical Reliability ◽  
Good Agreement

AbstractINTRODUCTIONThe development of fully automated immunoassay platforms has improved the technical reliability of cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.METHODSWe quantified Aβ1-42, Aβ1-40, tTau and pTau levels using the Lumipulse G System in 94 CSF samples from participants of the SPIN cohort with available 18F-Florbetapir imaging. Amyloid scans were assessed visually and through automated quantification. We determined the cutoffs of CSF biomarkers that optimized their agreement with 18F-Florbetapir PET and evaluated concordance between markers of the amyloid category.RESULTSAβ1-42, tTau and pTau (but not Aβ1-40) and the ratios with Aβ1-42 had good diagnostic agreement with 18F-Florbetapir PET. As a marker of amyloid pathology, the Aβ1-42/Aβ1-40 ratio had higher agreement and better correlation with amyloid PET than Aβ1-42 alone.DISCUSSIONCSF biomarkers measured with the Lumipulse G System show good agreement with amyloid imaging. Combination of Aβ1-42 with Aβ1-40 increases the agreement between markers of amyloid pathology.

scholarly journals Longitudinal Observation of Early-Onset Alzheimer’s Disease Dementia with Positive CSF Biomarkers/Negative Amyloid-β Positron-Emission Tomography

2021 ◽  
Vol 39 (3) ◽  
pp. 214-218
Author(s):  
Min Hye Kim ◽  
Joonho Lee ◽  
Hong Nam Kim ◽  
In Ja Shin ◽  
Keun Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Early Onset ◽  
Brain Magnetic Resonance Imaging ◽  
Amyloid Β ◽  
Emission Tomography ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Positron Emission

We report a 61-year-old woman with clinical course for Alzheimer’s disease (AD) dementia and discordant amyloid-β positron-emission tomography (PET) and cerebrospinal fluid biomarkers. Brain magnetic resonance imaging revealed remarkable atrophy in the hippocampus. However, repeated delayed <sup>18</sup>F-flutemetamol brain amyloid PET images with 1 year-interval revealed no amyloid deposition, whereas her CSF revealed low Aβ42, high total tau and p-tau181. This discordant amyloid-β PET and CSF biomarkers in this early-onset AD dementia might be associated with her low resilience or mixed pathology.

scholarly journals Associations of Fully Automated CSF and Novel Plasma Biomarkers With Alzheimer Disease Neuropathology at Autopsy

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012513
Author(s):  
Michel J. Grothe ◽  
Alexis Moscoso ◽  
Nicholas J. Ashton ◽  
Thomas K. Karikari ◽  
Juan Lantero-Rodriguez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Braak Stage ◽  
Neuritic Plaques ◽  
Neurofilament Light ◽  
T Tau

Objective:To study cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) analyzed by fully automated Elecsys immunoassays in comparison to neuropathologic gold standards, and compare their accuracy to plasma phosphorylated tau (p-tau181) measured using a novel Simoa method.Methods:We studied ante-mortem Elecsys-derived CSF biomarkers in 45 individuals who underwent standardized post-mortem assessments of AD and non-AD neuropathologic changes at autopsy. In a subset of 26 participants, we also analysed ante-mortem levels of plasma p-tau181 and neurofilament light (NfL). Reference biomarker values were obtained from 146 amyloid-PET-negative healthy controls (HC).Results:All CSF biomarkers clearly distinguished pathology-confirmed AD dementia (N=27) from HC (AUCs=0.86-1.00). CSF total-tau (t-tau), p-tau181, and their ratios with Aβ1-42, also accurately distinguished pathology-confirmed AD from non-AD dementia (N=8; AUCs=0.94-0.97). In pathology-specific analyses, intermediate-to-high Thal amyloid phases were best detected by CSF Aβ1-42 (AUC[95% CI]=0.91[0.81-1]), while intermediate-to-high CERAD neuritic plaques and Braak tau stages were best detected by CSF p-tau181 (AUC=0.89[0.79-0.99] and 0.88[0.77-0.99], respectively). Optimal Elecsys biomarker cut-offs were derived at 1097/229/19 pg/ml for Aβ1-42, t-tau, and p-tau181. In the plasma subsample, both plasma p-tau181 (AUC=0.91[0.86-0.96]) and NfL (AUC=0.93[0.87-0.99]) accurately distinguished pathology-confirmed AD (N=14) from HC. However, only p-tau181 distinguished AD from non-AD dementia cases (N=4; AUC=0.96[0.88-1.00]), and showed a similar, though weaker, pathologic specificity for neuritic plaques (AUC=0.75[0.52-0.98]) and Braak stage (AUC=0.71[0.44-0.98]) as CSF p-tau181.Conclusions:Elecsys-derived CSF biomarkers detect AD neuropathologic changes with very high discriminative accuracy in-vivo. Preliminary findings support the use of plasma p-tau181 as an easily accessible and scalable biomarker of AD pathology.Classification of Evidence:This study provides Class II evidence that fully-automated CSF t-tau and p-tau181measurements discriminate between autopsy-confirmed Alzheimer's disease and other dementias.

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