Menu
SENS PubMed Publication Search
Amyloid Precursor Protein CTF accumulates in synapses in sporadic and genetic forms of Alzheimer's disease
Paula Ferrer-Raventós 1 2, David Puertollano-Martín 1, Marta Querol-Vilaseca 1 2, Érika Sánchez-Aced 1 2, Natalia Valle-Tamayo 1, Alba Cervantes-Gonzalez 1 2, Raúl Nuñez-Llaves 1 2, Jordi Pegueroles 1 2, Oriol Dols-Icardo 1, Maria Florencia Iulita 1 2, Iban Aldecoa 3 4, Laura Molina-Porcel 3 5, Raquel Sánchez-Valle 3 5, Juan Fortea 1 2, Olivia Belbin 1 2, Sònia Sirisi 1 2, Alberto Lleó 1 2
Abstract:
Aims: Amyloid Precursor Protein (APP) -C-terminal fragment ( CTF) may have a neurotoxic role in Alzheimer´s disease (AD). CTF accumulates in the brains of patients with sporadic (SAD) and genetic forms of Alzheimer's Disease (AD). Synapses degenerate early during the pathogenesis of AD. We studied whether the CTF accumulates in synapses in SAD, autosomal dominant AD (ADAD) and Down syndrome (DS).
Methods: We used Array tomography to determine APP at synapses in human AD tissue. We measured CTF, A 40, A 42 and phosphorylated tau181 (p-tau181) concentrations in brain homogenates and synaptosomes of frontal and temporal cortex of SAD, ADAD, DS and controls.
Results: APP colocalized with pre- and post-synaptic markers in human AD brains. APP CTF was enriched in AD synaptosomes.
Conclusions: We demonstrate that CTF accumulates in synapses in SAD, ADAD and DS. This finding might suggest a role for CTF in synapse degeneration. Therapies aimed at mitigating CTF accumulation could be potentially beneficial in AD.
Methods: We used Array tomography to determine APP at synapses in human AD tissue. We measured CTF, A 40, A 42 and phosphorylated tau181 (p-tau181) concentrations in brain homogenates and synaptosomes of frontal and temporal cortex of SAD, ADAD, DS and controls.
Results: APP colocalized with pre- and post-synaptic markers in human AD brains. APP CTF was enriched in AD synaptosomes.
Conclusions: We demonstrate that CTF accumulates in synapses in SAD, ADAD and DS. This finding might suggest a role for CTF in synapse degeneration. Therapies aimed at mitigating CTF accumulation could be potentially beneficial in AD.
