Wiley, Neuropathology and Applied Neurobiology, 1(49), 2023
DOI: 10.1111/nan.12879
Full text: Unavailable
AbstractAimsAmyloid precursor protein (APP) đ˝âCâterminal fragment (đ˝CTF) may have a neurotoxic role in Alzheimer's disease (AD). đ˝CTF accumulates in the brains of patients with sporadic (SAD) and genetic forms of AD. Synapses degenerate early during the pathogenesis of AD. We studied whether the đ˝CTF accumulates in synapses in SAD, autosomal dominant AD (ADAD) and Down syndrome (DS).MethodsWe used array tomography to determine APP at synapses in human AD tissue. We measured đ˝CTF, Ađ˝40, Ađ˝42 and phosphorylated tau181 (pâtau181) concentrations in brain homogenates and synaptosomes of frontal and temporal cortex of SAD, ADAD, DS and controls.ResultsAPP colocalised with preâ and postâsynaptic markers in human AD brains. APP đ˝CTF was enriched in AD synaptosomes.ConclusionsWe demonstrate that đ˝CTF accumulates in synapses in SAD, ADAD and DS. This finding might suggest a role for đ˝CTF in synapse degeneration. Therapies aimed at mitigating đ˝CTF accumulation could be potentially beneficial in AD.