{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:10:27Z","timestamp":1790079027507,"version":"4.0.1"},"reference-count":12,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Anti-amyloid immunotherapies reduce amyloid-\u03b2 (A\u03b2) plaques but carry a 15\u201335% risk of amyloid-related imaging abnormalities (ARIA), particularly in APOE \u03b54\/\u03b54 carriers. This preliminary observational study evaluated blood A\u03b2 oligomer changes following treatment with the multi-component herbal formula Chongnoi-tang (CNT) and contextualized these findings against natural disease trajectories in National Alzheimer\u2019s Coordinating Center (NACC) and Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI) reference cohorts. Methods: This retrospective pilot cohort included 16 patients with Alzheimer\u2019s spectrum conditions treated with CNT. Blood A\u03b2 oligomers were measured using the AlzOn Plus immunoassay. Primary analysis (n = 13) excluded cases with a ceiling-level baseline value, an intercurrent potentially confounding condition, or no true baseline measurement. Results: Mean blood A\u03b2 oligomer levels decreased by 15.8% \u00b1 13.4% at 6 months (median \u221220.6%; 95% CI \u221223.9% to \u22127.8%; Wilcoxon signed-rank test, p &lt; 0.001; paired Cohen\u2019s dz = 1.07). At each participant\u2019s final available follow-up, all 13 primary-analysis patients had values below baseline. High-risk patients (n = 4) showed a mean 25.7% reduction. Baseline A\u03b2 level and 6-month percent biomarker change exhibited an exploratory, non-significant inverse trend in the Pearson correlation (r = \u22120.489, p = 0.090) that was weaker and non-significant in the Spearman sensitivity analysis (\u03c1 = \u22120.300, p = 0.320), consistent with regression to the mean and mathematical coupling as plausible contributors. Importantly, all four APOE \u03b54\/\u03b54 homozygotes showed A\u03b2 reductions without ARIA-like clinical events. Mini-Mental State Examination (MMSE) worsening occurred in 37.5% (3\/8) of CNT-treated patients versus 42.9% (15\/35) in propensity-matched NACC controls (p = 0.89); given the small sample, this comparison is inconclusive. Conclusions: In this small, uncontrolled pilot study, CNT was associated with blood A\u03b2 reductions, which should be interpreted as a statistical association rather than confirmed evidence of a treatment effect; no treatment discontinuations due to adverse effects were documented in this small cohort, including among APOE \u03b54\/\u03b54 carriers. These hypothesis-generating findings warrant further confirmation in prospective randomized controlled trials.<\/jats:p>","DOI":"10.3390\/jcm15187329","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"7329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood Amyloid-\u03b2 Reduction Following Chongnoi-tang Treatment in Alzheimer\u2019s Spectrum Conditions: A Retrospective Pilot Observational Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6781-8720","authenticated-orcid":false,"given":"Jinhyuk","family":"Lee","sequence":"first","affiliation":[{"name":"Chongnoi Korean Medical Clinic, Seoul 06541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Disease International (2015). 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