O1-07-01: Diagnostic comparison of regional amyloid PET and different CSF biomarker assays for identifying early Alzheimer's disease

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.

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Plasma Aβ 42:40 ratio tracks with changes in brain amyloid PET SUVr in the core and open label extension of the phase 2 proof of concept study ban2401‐g000‐201 following treatment with lecanemab in subjects with early Alzheimer’s disease

Alzheimer s & Dementia ◽

10.1002/alz.057760 ◽

2021 ◽

Vol 17 (S9) ◽

Author(s):

Chad J Swanson ◽

Michio Kanekiyo ◽

June Kaplow ◽

Shobha Dhadda ◽

Michael C Irizarry ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Pet ◽

Phase 2 ◽

Proof Of Concept ◽

Open Label ◽

Concept Study ◽

The Core ◽

Open Label Extension ◽

Early Alzheimer’S Disease

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P4-257: Accurate early Alzheimer's disease detection: Cross-tracer validation of automated voxel-based amyloid PET SUVR in independent datasets

Alzheimer s & Dementia ◽

10.1016/j.jalz.2015.08.086 ◽

2015 ◽

Vol 11 (7S_Part_19) ◽

pp. P880-P880 ◽

Cited By ~ 1

Author(s):

Arthur Mikhno ◽

Janos Redei ◽

John Mann ◽

Ramin Parsey

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Detection ◽

Amyloid Pet ◽

Early Alzheimer’S Disease

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Subgroup analyses of the amyloid PET substudies from EMERGE and ENGAGE, phase 3 clinical trials evaluating aducanumab in patients with early Alzheimer’s disease

Alzheimer s & Dementia ◽

10.1002/alz.057496 ◽

2021 ◽

Vol 17 (S9) ◽

Author(s):

Raj Rajagovindan ◽

Tianle Chen ◽

Hao Wu ◽

Ying Tian ◽

Laura Nisenbaum ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Amyloid Pet ◽

Phase 3 ◽

Subgroup Analyses ◽

Early Alzheimer’S Disease

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A THREE-RANGE APPROACH ENHANCES PROGNOSTIC UTILITY OF CSF BIOMARKERS IN ALZHEIMER’S DISEASE

10.5327/1980-5764.rpda022 ◽

2021 ◽

Author(s):

Wagner Brum ◽

Andrei Bieger ◽

Joao Pedro Ferrari- Souza ◽

Marco de Bastiani ◽

Andrea Benedet ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Csf Biomarkers ◽

Amyloid Pet ◽

Operating Characteristics ◽

Csf Biomarker ◽

Prognostic Utility ◽

Power Analyses

Background: Alzheimer’s disease (AD) was biologically defined by the 2018 NIA-AA Research Framework (RF), which recommends dichotomously defining biomarker status as normal or abnormal with single cutpoints. However, a three-range approach remains unexplored in AD fluid biomarkers. Objective: To assess the prognostic utility of a three-range approach for CSF biomarkers in AD. Methods: We included 1278 non-demented individuals (CU: n=575; MCI: n=703) from the ADNI with baseline CSF Elecsys® biomarkers. Within it, we defined three-range cutpoints with two-graph receiver operating characteristics (TGROC) for each CSF biomarker (Aβ1-42, p-tau, p-tau/Aβ1-42), based on amyloid PET positivity. Then, linear mixed-effects and Cox proportional hazards models were used to estimate longitudinal cognitive trajectories and risk of clinical progression based on CSF biomarker status. Hereby derived three-range cutpoints were compared to previously described binary thresholds for the same biomarkers. Power analyses for simulated trials were also carried. Results: We observed dynamic amyloid-PET changes for participants in the intermediate range, while a static profile for clearly normal and abnormal groups. Longitudinally, our approach revealed a divergent intermediate cognitive trajectory undetected by dichotomization, with power analyses demonstrating potential applications for trial enrichment. Conclusion: The proposed approach can improve CSF-based diagnosis, refine prognostic assessment and enhance clinical trial recruitment.

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