Plasma biomarker trajectories across Alzheimer’s clinical onset: a 17-year prospective study
Year: 2026
Type: article
Abstract: BACKGROUND: Long-term trajectories of plasma biomarkers relative to clinical symptom onset in Alzheimer’s disease (AD) remain scarce. METHODS: We analyzed 17-year longitudinal data from 195 initially cognitively unimpaired participants in the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) study. Plasma biomarker trajectories were modeled as a function of years from estimated mild cognitive impairment (MCI) symptom onset using generalized additive mixed models. RESULTS: In participants who progressed to amyloid-positive MCI, plasma p-tau181/Aβ42 and GFAP diverged from stable controls earliest (about 13 and 12 years before symptom onset, respectively), followed by Aβ42/Aβ40, p-tau181, and NfL, all of which became abnormal before symptom onset. Individuals who developed amyloid-negative MCI showed abnormalities only in GFAP (about 11 years before onset) and YKL-40 (around the time of symptom onset). CONCLUSIONS: This study establishes a clinically anchored temporal map of plasma AD biomarkers. Plasma markers detect AD-related pathological changes more than a decade before symptom onset, offering a scalable, non-invasive approach for defining the preclinical phase and identifying at-risk individuals for early intervention.
Source: Alzheimer s Research & Therapy
Authors: Siqi Xie, Yumei Liang, Yana Pang, Ying Li, Shuman Cao, Yan Li, Qi Wang, Abhay Moghekar, Marilyn Albert, Jianping Jia, BIOCARD Study team, Barbara Rodzon, Anja Soldan, Corinne Pettigrew, Leonie Farrington, Maura Grega, Michael Miller, Susumu Mori, Tilak Ratnanather, Anthony Kolasny, Hanzhang Lu, Kenichi Oishi, Laurent Younes, Sara Grace Ho, David Shade, Ann Ervin, Jennifer Jones, Hamadou Coulibaly, Mei-Cheng Wang, Yuxin Zhu, Jiangxia Wang, Juan Troncoso, David Nauen
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,290
Funder: National Institute on Aging
OpenAlex ID: W7155035526