Amyloid precursor protein βCTF accumulates in synapses in sporadic and genetic forms of Alzheimer’s disease

Amyloid precursor protein βCTF accumulates in synapses in sporadic and genetic forms of Alzheimer’s disease

The main pathological features observed in a brain with Alzheimer’s disease (AD) are the accumulation of β-amyloid (Aβ) peptides in the form of plaques and the aggregation of phosphorylated tau protein. Amyloid precursor protein (APP) can be processed via the amyloidogenic pathway and the non-amyloidogenic pathway. From the amyloidogenic pathway, APP is cleaved by the action of β-secretase generating a β-C-terminal fragment (βCTF). Subsequently, γ-secretase cleaves this βCTF and releases the Aβ peptides, generating amyloid plaques.

What have been done in this study, and what are the main results?

Array Tomography has shown, in human brain tissue, that the APP protein is localised in the synapse and that it forms a neuritic pattern in cases of autosomal-dominant AD and Down’s Syndrome.

On the other hand, in synaptosomes enriched fractions of frontal and temporal cortex from postmortem tissue of people with sporadic AD, familial AD and Down’s Syndrome, it has been described that there is an increase in the accumulation of these βCTF fragments at the synapse in the sporadic form and in the genetic forms (autosomic-dominant AD and Down’s Syndrome) compared to healthy controls.

Relevance of the study

The results of this study extend the data on the relevance of these βCTF fragments as pathological components of the sporadic and genetic forms of AD. of AD. Evidence of toxic accumulation of these fragments could support further research directed at this fragment as a therapeutic target.

More information

https://pubmed.ncbi.nlm.nih.gov/36702749/

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