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bioRxiv · 10.1101/2022.09.13.507759

APP family member dimeric complexes are formed predominantly in synaptic compartments

Schilling, S.·August, A.·Meleux, M.·Conradt, C.·Tremmel, L.·Teigler, S.·Koo, E. H.·Kins, S.·Eggert, S.
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Abstract

The amyloid precursor protein (APP), a key player in Alzheimes disease (AD), is part of a larger gene family, including the APP like proteins APLP1 and APLP2. They share similar structures, form homo- and heterotypic dimers and exhibit overlapping functions. We investigated complex formation of the APP family members via two inducible dimerization systems, the FKBP-rapamycin based dimerization as well as cysteine induced dimerization, combined with coimmunoprecipitations and Blue Native (BN) gel analyses. Within the APP family, APLP1 shows the highest degree of dimerization and high molecular weight (HMW) complex formation. Interestingly, about 20% of APP is dimerized in cultured cells while about 50% of APP is dimerized in mouse brains, independent of age and splice forms. Furthermore, we could show that dimerized APP originates mostly from neurons and is enriched in synaptosomes. Finally, BN gel analysis of human cortex samples shows a significant decrease of APP dimers in AD patients compared to controls, suggesting that loss of dimers of full-length APP might correlate with loss of synapses in the process of AD.

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Schilling, S., August, A., Meleux, M., Conradt, C., Tremmel, L., Teigler, S., Koo, E. H., Kins, S., Eggert, S.. 2022-09-16. APP family member dimeric complexes are formed predominantly in synaptic compartments. https://doi.org/10.1101/2022.09.13.507759

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