Ten-Year Disease Control of Metastatic Pancreatic Neuroendocrine Tumour Treated With Everolimus.

Alzheimer’s disease (AD) is a chronically progressive neurodegenerative condition characterized by worsening cognition, synaptic impairment, and extensive neuronal degeneration (). Although extracellular amyloid-β (Aβ) deposits and intraneuronal aggregates of hyperphosphorylated tau are well-established pathological lesions and central hallmarks of AD, pathological changes can develop silently for 15–20 years before symptoms become clinically evident (; ). This long preclinical phase underscores the need to identify additional biomarkers and mechanisms beyond amyloid and tau pathology. Emerging evidence has implicated clathrin-mediated endocytosis (CME) in AD pathogenesis (; ). Genome-wide association studies have implicated CME-related genes, such as BIN1 and PICALM, as key contributors to AD susceptibility (, ; ). Experimental studies have further shown that CME regulates amyloid precursor protein (APP) internalization and Aβ generation and may also influence tau propagation (; ). Although CME research has largely focused on its core components, emerging evidence suggests that alterations in accessory proteins could substantially influence CME function, particularly in neurons (). Among these accessory proteins, Amphiphysin-1 (AMPH) appears particularly relevant to AD. AMPH, a critical CME accessory protein, promotes vesicle scission by sensing membrane curvature via its BAR domain and recruiting dynamin via its SH3 domain (; ). Recent clinical studies have shown that AMPH expression is markedly decreased in the temporal and frontal cortices (). In the JNPL3 mouse model, which is characterized by pathological tau overexpression (), brain regions with substantial tau aggregation show markedly reduced AMPH protein levels (). AMPH-knockout mice exhibit severe neuropathological features, including synaptic dysfunction, seizures, and learning impairments (). Although AMPH expression appears reduced in brain tissue across human and animal studies, CSF AMPH levels have conversely been reported to be elevated in AD patients (). Together, these findings suggest that CSF AMPH may reflect AD-related processes, but its relationship with established biomarkers and disease progression remains unclear. On the basis of prior studies (; ), AMPH was prespecified before the current analyses as a hypothesis-driven candidate protein in the present study. Therefore, we aimed to (1) compare CSF AMPH levels across groups defined by clinical diagnosis and AT(N) biomarker profiles; (2) evaluate associations between CSF AMPH and core AD biomarkers (CSF amyloid-β [Aβ], phosphorylated tau [P-tau], and total tau [T-tau]); and (3) examine associations between CSF AMPH and cognitive performance, as well as whether baseline CSF AMPH was associated with longitudinal cognitive change and the risk of clinical progression.