Estimated onset age of CSF amyloid and tau accumulation and relationship to clinical outcomes - Poster Presentation

Q: What does the study estimate about CSF biomarkers?

It estimates the onset ages of accelerated CSF amyloid (AB42/AB40) and tau (p-tau181) accumulation using a biomarker change-point approach in initially cognitively unimpaired participants.

Q: How does APOE-e4 status affect estimated onset age and biomarker changes?

APOE-e4 carriers show approximately 6 years earlier EABA for both amyloid and tau, and Cox regression indicates shorter time to EABA for APOE-e4 carriers.

Q: Do estimated onset ages relate to when participants develop MCI symptoms?

Yes. Older EABAs are associated with a shorter time to MCI symptom onset, and EABA precedes MCI symptom onset by about 24 years on average.

Sep 30, 2026

Uploaded by Stanley

Background: Neuropathological evidence indicates Alzheimer’s disease pathology emerges in midlife, yet few studies quantify when CSF biomarker changes begin simultaneously for amyloid and tau. This poster evaluates estimated onset ages of CSF AB42/AB40 and p-tau181 accumulation (EABA), identifies factors driving EABA variability, and tests whether EABA predicts progression to MCI clinical symptoms. Methods: CSF AB42/AB40 and p-tau181 were analyzed using Lumipulse assays in BIOCARD participants followed over 8.6 years. Results show earlier EABA in APOE-e4 carriers and faster biomarker change slopes with EABA, with EABA relating to earlier MCI symptom onset.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages3

Reading Time8 min

AccessFree to download

Abstract

Background

Method

Result

Conclusion

DOI: 10. 1002/alz70856_105770 BIOMARKERS POSTER PRESENTATION BIOMARKERS (NON-NEUROIMAGING) Estimated onset age ofCSF amyloid and tau accumulation and relationship to clinical outcomes Corinne Pettigrew1 Marilyn S. S. Albert 1 Yuxin Zhu 1 Anja Soldan2 Abhay Moghekar 1 Mei-Cheng Wang3 1Johns Hopkins University School of Medicine, Baltimore, MD, USA 2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Correspondence Corinne Pettigrew, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [Email:](Email: cpettigrew@jhmi.edu)[ cpettigrew@jhmi.edu](Email: cpettigrew@jhmi.edu) Abstract Background: Neuropathological studies indicate AD pathology is present in midlife. Few studies, however, have examined the onset of AD biomarker changes, simultaneously for amyloid and tau, starting in midlife. Using data from initially cognitively unimpaired, primarily middle-aged participants, we evaluated: 1) the‘change point’ that marks accelerated accumulation of CSF AB42/AB40 and p-tau181 and estimated onset ages of biomarker accumulation (EABA); 2) factors impacting EABA variability, and 3) association of EABA with risk of progression to MCI clinical symptoms. Method: Analyses evaluated CSF AB42/AB40 and p-tau181 (Fujirebio Lumipulse G1200 assays) in N = 384 cognitively unimpaired BIOCARD Study participants (M baselineage=58.4y, 58% female;M = 3. 2 CSF measures collected over 8.6y). Biomarker ‘change points’ were identified (in the 62% with ≥2 CSF measures) and EABA calculated for AB42/AB40 and p-tau181 using methods previously applied to amyloid PET (Schindler et al., 2021). Result: The mean EABA for AB42/AB40 was 49.3 years vs. 51.6 for p-tau181 ; EABAs were ∼6y earlier for APOE-e4 carriers vs. non-carriers (Table 1, Figure 1). Participants with an EABA demonstrated steeper CSF biomarker changes over time, compared to participants without an EABA (Figure 2). In Cox regression models, APOE-e4 carriers had a shorter time to EABA for both AB42/AB40 (HR=3.65, p <0.01) and p-tau181 (HR=2.00, p <0.01). In Cox models including the subset of participants with EABAs, older EABAs (but not APOE-e4, sex, or education) were associated with a shorter time to MCI symptom onset (AB40/AB40 HR=2.12, p <0.01; p-tau181 HR=3.34, p <0.01); additionally, for AB40/AB40 , the association of EABA with symptom onset accelerated (became increasingly shorter) at older EABAs (HR for EABA2 = 1. 35, p <0.01). EABA preceded MCI symptom onset by 24 years, on average (SD=8-11). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e105770. [https://doi.org/10.1002/alz70856_105770](https://doi.org/10.1002/alz70856_105770) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of3 BIOMARKERS Conclusion: Results indicate that AD CSF biomarker changes begin in midlife, decades before MCI clinical symptom onset. They are consistent with the view that both amyloid and tau onset occurs earlier in APOE-e4 carriers, with additional analyses needed to evaluate whether APOE-e4-related changes in p-tau181 are due to APOEe4-related AB42/AB40 changes. Lastly, the shorter time to symptom onset with older EABAs suggest that co-pathologies (which are greater at older ages) may reduce the time from biomarker accumulation to symptom onset. BIOMARKERS

FAQs

What does the study estimate about CSF biomarkers?

It estimates the onset ages of accelerated CSF amyloid (AB42/AB40) and tau (p-tau181) accumulation using a biomarker change-point approach in initially cognitively unimpaired participants.

How does APOE-e4 status affect estimated onset age and biomarker changes?

APOE-e4 carriers show approximately 6 years earlier EABA for both amyloid and tau, and Cox regression indicates shorter time to EABA for APOE-e4 carriers.

Do estimated onset ages relate to when participants develop MCI symptoms?

Yes. Older EABAs are associated with a shorter time to MCI symptom onset, and EABA precedes MCI symptom onset by about 24 years on average.

Sep 30, 2026

Uploaded by Stanley