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The Role of Presenilins in Aβ-Induced Cell Death in Alzheimer’s Disease

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Book cover Abeta Peptide and Alzheimer’s Disease

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Abstract

Neuronal death in specific brain regions is a common feature of neurodegenerative disorders. Alzheimer’s disease (AD) is characterized by synaptic loss and a substantial amount of neuronal degeneration in regions involved in memory and learning processes (e.g., temporal, entorhinal and frontal cortex; hippocampus). The neuropathologic hallmarks of AD include the accumulation of amyloid plaques and hyperphosphorylated tau forming intracellular tangles. However, no correlation has been established between the number of plaques and the cognitive performance in AD patients [1], [2]. Instead, synaptic failure and intracellular production of amyloid beta (Aβ) appears to correlate well with the early cognitive dysfunction in AD patients [3], [4]. This has also been tested in a triple transgenic mouse model of AD where accumulation of intracellular Aβ1–42 corresponded with the early cognitive impairment [5]. Interestingly, no extracellular deposits of Aβ1–42 were detected in these mice at 4 months of age suggesting that A–1–42 accumulate intracellulary early in the disease process. Moreover, intracellular accumulation of Aβ1–42 was cleared with administration of anti-Aβ antibodies and rescued the retention deficits seen in young 3×Tg AD mice. Together, results from this and several other studies indicate that intracellular Aβ1–42-generation causes the primary toxicity to neurons in AD [6].

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  1. Section for Experimental Geriatrics, Karolinska Institutet Neurotec, Huddinge, Sweden

    Maria Ankarcrona PhD

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  1. Research and Development, Ocean Nutrition Canada, Dartmouth, Nova Scotia, Canada

    Colin J. Barrow BSc (Hons),PhD, MBA (Vice President) (Vice President)

  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

    David H. Small BSc, PhD (Associate Professorial Fellow) (Associate Professorial Fellow)

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Ankarcrona, M. (2007). The Role of Presenilins in Aβ-Induced Cell Death in Alzheimer’s Disease. In: Barrow, C.J., Small, D.H. (eds) Abeta Peptide and Alzheimer’s Disease. Springer, London. https://doi.org/10.1007/978-1-84628-440-3_14

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  • DOI: https://doi.org/10.1007/978-1-84628-440-3_14

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