Summary
Alzheimer’s disease is the most common form of dementia. About 90% of the cases occur sporadically whereas in 10% of the cases mutations were found within three different genes. Mutations in the gene encoding the β-Amyloid precursor protein (βAPP) are located in the ultimate neighborhood of the three proteases (secretases) involved in proteolytic processing of βAPP. These mutations cause an increased production of the long form of Amyloid β-peptide (Aβ) the major component of Amyloid plaques. In contrast to the 40 amino acid form (Aβ40), the 42 amino acid form (Aβ42) aggregates more rapidly, kills cultured neurons more efficiently, and precipitates preferentially in amyloid plaques. Interestingly, mutations in the Presenilin genes which are responsible for more then 40% of all familial AD cases also cause enhanced production of the elongated form of Aβ. Therefore mutations in three different genes directly effect Aβ production in a pathological manner, which strongly supports the amyloid cascade hypothesis.
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Haass, C., Baumeister, R. (1998). What do we learn from a few familial Alzheimer’s disease cases?. In: Gertz, HJ., Arendt, T. (eds) Alzheimer’s Disease — From Basic Research to Clinical Applications. Journal of Neural Transmission. Supplementa, vol 54. Springer, Vienna. https://doi.org/10.1007/978-3-7091-7508-8_13
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DOI: https://doi.org/10.1007/978-3-7091-7508-8_13
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