학술논문
Amyloid precursor protein 훽CTF accumulates in synapses in sporadic and genetic forms of Alzheimer's disease.
Document Type
Article
Author
Ferrer‐Raventós, Paula; Puertollano‐Martín, David; Querol‐Vilaseca, Marta; Sánchez‐Aced, Érika; Valle‐Tamayo, Natalia; Cervantes‐Gonzalez, Alba; Nuñez‐Llaves, Raúl; Pegueroles, Jordi; Dols‐Icardo, Oriol; Iulita, Maria Florencia; Aldecoa, Iban; Molina‐Porcel, Laura; Sánchez‐Valle, Raquel; Fortea, Juan; Belbin, Olivia; Sirisi, Sònia; Lleó, Alberto
Source
Subject
Language
ISSN
0305-1846
Abstract
Aims: Amyloid precursor protein (APP) 훽‐C‐terminal fragment (훽CTF) may have a neurotoxic role in Alzheimer's disease (AD). 훽CTF 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 훽CTF 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 훽CTF, A훽40, A훽42 and phosphorylated tau181 (p‐tau181) concentrations in brain homogenates and synaptosomes of frontal and temporal cortex of SAD, ADAD, DS and controls. Results: APP colocalised with pre‐ and post‐synaptic markers in human AD brains. APP 훽CTF was enriched in AD synaptosomes. Conclusions: We demonstrate that 훽CTF accumulates in synapses in SAD, ADAD and DS. This finding might suggest a role for 훽CTF in synapse degeneration. Therapies aimed at mitigating 훽CTF accumulation could be potentially beneficial in AD.Using array tomography in post‐mortem brain tissue from the temporal and frontal cortex, we found that APP is located in synaptic compartments in different forms of AD. We also describe that APP βCTF accumulates in synaptosomal fractions in different forms of AD and that this accumulation correlates with Aβ and tau concentrations. [ABSTRACT FROM AUTHOR]