Abstract

Various and different peptides products resulting from enzymatic protein cleavage of Amyloid Precursor Proteins (APP) are the main agents in the pathophysiology of Alzheimer’s disease (AD). Although relatively well-known, they still arouse interest leading to further intense and wide-ranging research. Their biology and physico-chemical properties still are challenging for basic, experimental research and are matter of scientific debate. The APP itself and its functions are still somewhat enigmatic and therefore it is also called the All Purpose Protein. Apart from well known amyloidogenic and antiamyloidogenic (non-amyloidogenic) enzymatic cleavage pathways of APP protein this paper deals with issues connected with other, alternative pathways that seem to be interesting and important as well. They lead to other than Aβ forms of peptide products such as: N-APP, N-terminally cleavage products of APP (N-terminally truncated ) Aβ’, γ- secretase-independent pathway products that involve concerted cleavages of APP by α- and β-secretase or products that emerge after caspase activity. Presence of all these peptides in CSF, ISF, blood serum and urine of the AD patients is crucial for successful diagnosis, giving rise to hope of their better detection and potentially better treatment of AD. Therefore, newly discovered products of the AβT domain cleavage (Aβ total i.e. full fibrillating domain of APP), Aβ type products and other peptides because of their biology and physico-chemical properties are very intriguing and deserve further experimental research. On the other hand after better recognition and better understanding their biology they might be enormously useful in the future for diagnosis and therapy for example Alzheimer’s disease.

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