Abstract Details

Title Real-world Characterization of CSF Alzheimer’s Disease Staging Biomarkers (pT217, pT205, MTBR-tau243) in Thai Memory Clinics

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 13-002

Objective This study aimed to characterize CSF AD staging biomarkers measured using locally performed mass spectrometry and commercial reagents in real-world memory clinic populations.

Background As disease-modifying therapies become standard care for Alzheimer’s disease (AD), there is increasing demand for reliable staging biomarkers (“Core 2,” e.g., tau-PET). However, tau-PET is costly and often unavailable, especially in low- and middle-income settings. Fluid biomarkers offer a scalable alternative, but their reproducibility remains understudied.

Design/Methods CSF samples were collected from two memory clinics in Bangkok, Thailand. Multiple tau species were simultaneously quantified using immunoprecipitation liquid chromatography–tandem mass spectrometry (IP–MS/MS) at the Laboratory of Biochemistry, Chulabhorn Research Institute. CSF IP–MS/MS-based pT217, pT205, and MTBR-tau243 levels were compared between AD and non-AD participants, defined by CSF Aβ42/p-tau181 (“Core 1”), and across clinical stages (CU/SCD, MCI, dementia). Mediation analyses were performed to examine hierarchical relationships among biomarkers and their dependency on Aβ42/p-tau181. Gaussian mixture models (GMM) were used to binarize biomarkers and assess stage distributions.

Results Among 59 participants (median age 72 years [IQR 63–77]; 63% female; 42% dementia; 46% AD), CSF pT217, pT205, and MTBR-tau243 were elevated in AD versus non-AD (all p<0.001; AUC 0.99, 0.92, and 0.84, respectively). All biomarkers correlated with CSF Aβ42/p-tau181 after adjustment for age and sex, but only pT217 correlated with Aβ42/40. Biomarker levels increased stepwise with advancing clinical stage (all p<0.05, Kruskal–Wallis). Pairwise comparisons (Benjamini–Hochberg adjusted) showed significant CU/SCD–dementia differences for pT205 and MTBR-tau243 but not pT217. Mediation analyses revealed a hierarchical relationship: pT217 fully mediated Aβ42/p-tau181 effects on pT205 and MTBR-tau243; pT205 trended towards mediating MTBR-tau243. GMM classification showed 31% pT217+/pT205–, none pT217–/pT205+, and similar patterns for MTBR-tau243.

Conclusions CSF staging biomarkers exhibit sequential, hierarchical changes (pT217 → pT205 → MTBR-tau243) aligned with clinical progression and robust across settings and measurement methods. Future studies should evaluate their correspondence with tau-PET.

Authors/Disclosures
Watayuth Luechaipanit PRESENTER	Mr. Luechaipanit has nothing to disclose.
Thanaporn Haethaisong, Ms (Genetics)	Miss Haethaisong has nothing to disclose.
Adipa Chongsuksantikul, DEng	Dr. Chongsuksantikul has nothing to disclose.
Prawit Oangkhana, MS	Mr. Oangkhana has nothing to disclose.
Jedsada Khieukhajee, MD	The institution of Dr. Khieukhajee has received research support from Thailand Science Research and Innovation (TSRI).
Thanakit Pongpitakmetha (Department of Pharmacology, Faculty of Medicine, Chulalongkorn University)	Mr. Pongpitakmetha has nothing to disclose.
Chantragan Srisomsap, Sr., PhD	Dr. Srisomsap has nothing to disclose.
Daranee Chokchaichamnankit	Ms. Chokchaichamnankit has nothing to disclose.
Jisnuson Svasti, PhD	Prof. Svasti has nothing to disclose.
Poosanu Thanapornsangsuth (Thai Red Cross Emerging Infectious Diseases - Health Science Centre)	Poosanu Thanapornsangsuth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai.

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