Amyloid precursor protein ð½CTF accumulates in synapses in sporadic and genetic forms of Alzheimer's disease.
Neuropathol Appl Neurobiol
; 49(1): e12879, 2023 02.
Article
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| MEDLINE
| ID: mdl-36702749
ABSTRACT
AIMS:
Amyloid precursor protein (APP) ð½-C-terminal fragment (ð½CTF) may have a neurotoxic role in Alzheimer's disease (AD). ð½CTF 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 ð½CTF 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 ð½CTF, Að½40, Að½42 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 ð½CTF was enriched in AD synaptosomes.CONCLUSIONS:
We demonstrate that ð½CTF accumulates in synapses in SAD, ADAD and DS. This finding might suggest a role for ð½CTF in synapse degeneration. Therapies aimed at mitigating ð½CTF accumulation could be potentially beneficial in AD.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Síndrome de Down
/
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Revista:
Neuropathol Appl Neurobiol
Año:
2023
Tipo del documento:
Article
País de afiliación:
España