Pan Feng-Feng, Huang Lin, Wang Ying, Huang Qi, Guan Yi-Hui, Li Yue-Hua, Xie Fang, Guo Qi-Hao
Department of Gerontology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Alzheimers Dement. 2025 Dec;21(12):e70987. doi: 10.1002/alz.70987.
Blood-based phosphorylated tau 217 (p-tau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) show promise for Alzheimer's disease (AD), while their links to brain amyloid beta (Aβ)/tau, hippocampal atrophy, and cognitive decline need further investigation.
A cohort of 1275 participants, representing various cognitive stages, was recruited to examine the links between plasma biomarkers and brain Aβ/tau stages, tau progression, hippocampal atrophy, and cognitive decline.
Plasma p-tau217 effectively distinguished A-T-/A-T+ individuals and A+T+ patients, though it identified early A+T-/A+T+ stages only in Aβ+ subjects. Plasma GFAP levels plateau beyond a certain tau threshold, while Aβ-induced tau progression occurred only in those with high GFAP. Plasma NfL showed a weak link to brain Aβ and tau pathology, hippocampal atrophy, and typical AD cognitive decline.
Plasma p-tau217 aids in disease stratification, and GFAP promotes tau progression, while NfL is inadequate as a neuronal injury biomarker for AD.
Plasma p-tau217 is strongly linked to brain Aβ/tau burdens and effectively differentiates between various Aβ/tau stages. Elevated plasma levels of GFAP consistently contributed to the Aβ-induced tau progression across various Braak stages. Plasma NfL exhibits limited associations with Aβ/tau pathology, AD-specific hippocampal atrophy, and cognitive decline.
