Work

Association of cerebrospinal fluid amphiphysin-1 levels with cognition and Alzheimer’s disease pathology biomarkers

Year: 2026

Type: article

Abstract: Introduction Amphiphysin-1 (AMPH), an accessory component of the clathrin-mediated endocytosis (CME) machinery, plays a critical role in synaptic vesicle recycling and membrane dynamics and has been implicated in Alzheimer’s disease (AD) risk. However, its relationship with core AD biomarkers and disease progression remains unclear. Methods In this study, we examined the associations between cerebrospinal fluid (CSF) AMPH and core AD biomarkers (CSF amyloid-β42 [Aβ 42 ], phosphorylated tau [P-tau], and total tau [T-tau]), cognitive performance, neurodegeneration, and clinical progression in 723 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants were categorized according to the AT(N) framework into stage 0, stage 1, stage 2, and suspected non-AD pathophysiology (SNAP). Results AMPH exhibited stage-dependent alterations across the AD continuum, characterized by lower levels in stage 1, and elevated levels in stage 2 and SNAP. Cross-sectionally, CSF AMPH was positively associated with core CSF biomarkers. Longitudinal analyses showed that, among amyloid-negative individuals, higher baseline AMPH was associated with faster decreases in CSF Aβ 42 and increases in P-tau and T-tau. In the overall cohort, higher baseline AMPH was associated with accelerated hippocampal atrophy and cognitive decline, and with an increased risk of clinical progression (HR = 1.21, 95% CI: 1.05–1.37). Discussion In ADNI, CSF AMPH was associated with biological changes across the AD continuum, cognitive decline, hippocampal atrophy, and clinical progression. These findings may provide complementary information for understanding disease progression.

Source: Frontiers in Aging Neuroscience

DOI: 10.3389/fnagi.2026.1875646