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- W2891702111 startingPage "383" @default.
- W2891702111 abstract "Alzheimer's disease (AD) is a complex, multifactorial disease involving many pathological mechanisms. Nonetheless, single pathogenic mutations in amyloid precursor protein (APP) or presenilin 1 or 2 can cause AD with almost all of the clinical and neuropathological features, and therefore, we believe an important mechanism of pathogenesis in AD could be revealed from examining pathogenic APP missense mutations. A comprehensive review of the literature, including clinical, neuropathological, cellular and animal model data, was conducted through PubMed and the databases of Alzforum mutations, HGMD, UniProt, and AD&FTDMDB. Pearson correlation analysis combining the clinical and neuropathological data and aspects of mutant APP processing in cellular models was performed. We find that an increase in Aβ42 has a significant positive correlation with the appearance of neurofibrillary tangles (NFTs) and tends to cause an earlier age of AD onset, while an increase in Aβ40 significantly increases the age at death. The increase in the α-carboxyl terminal fragment (CTF) has a significantly negative correlation with the age of AD onset, and β-CTF has a similar effect without statistical significance. Animal models show that intracellular Aβ is critical for memory defects. Based on these results and the fact that amyloid plaque burden correlates much less well with cognitive impairment than do NFT counts, we propose a snowball hypothesis: the accumulation of intraneuronal NFTs caused by extracellular Aβ42 and the increase in intraneuronal APP proteolytic products (CTFs and Aβs) could cause cellular organelle stress that leads to neurodegeneration in AD, which then resembles the formation of abnormal protein snowballs both inside and outside of neurons." @default.
- W2891702111 created "2018-09-27" @default.
- W2891702111 creator A5029695887 @default.
- W2891702111 creator A5055357204 @default.
- W2891702111 creator A5063422539 @default.
- W2891702111 date "2019-01-01" @default.
- W2891702111 modified "2023-10-16" @default.
- W2891702111 title "Processing of Mutant β-Amyloid Precursor Protein and the Clinicopathological Features of Familial Alzheimer’s Disease" @default.
- W2891702111 cites W130950611 @default.
- W2891702111 cites W1486013008 @default.
- W2891702111 cites W1487107835 @default.
- W2891702111 cites W1518693759 @default.
- W2891702111 cites W1572812739 @default.
- W2891702111 cites W1602771322 @default.
- W2891702111 cites W1619610860 @default.
- W2891702111 cites W1805795852 @default.
- W2891702111 cites W1841850981 @default.
- W2891702111 cites W1866663684 @default.
- W2891702111 cites W1907506524 @default.
- W2891702111 cites W1942777675 @default.
- W2891702111 cites W1946603937 @default.
- W2891702111 cites W1964273058 @default.
- W2891702111 cites W1965351431 @default.
- W2891702111 cites W1968366631 @default.
- W2891702111 cites W1968780740 @default.
- W2891702111 cites W1968937229 @default.
- W2891702111 cites W1968995509 @default.
- W2891702111 cites W1969099023 @default.
- W2891702111 cites W1970363870 @default.
- W2891702111 cites W1971453970 @default.
- W2891702111 cites W1973391728 @default.
- W2891702111 cites W1975211057 @default.
- W2891702111 cites W1979025881 @default.
- W2891702111 cites W1980906872 @default.
- W2891702111 cites W1983591185 @default.
- W2891702111 cites W1984009511 @default.
- W2891702111 cites W1984300869 @default.
- W2891702111 cites W1985323612 @default.
- W2891702111 cites W1985945455 @default.
- W2891702111 cites W1988861131 @default.
- W2891702111 cites W1992116441 @default.
- W2891702111 cites W1992861152 @default.
- W2891702111 cites W1995344309 @default.
- W2891702111 cites W1995426930 @default.
- W2891702111 cites W1996173495 @default.
- W2891702111 cites W1996447834 @default.
- W2891702111 cites W1996772579 @default.
- W2891702111 cites W1997417397 @default.
- W2891702111 cites W2000350064 @default.
- W2891702111 cites W2001210466 @default.
- W2891702111 cites W2001618696 @default.
- W2891702111 cites W2001854231 @default.
- W2891702111 cites W2002821199 @default.
- W2891702111 cites W2005452561 @default.
- W2891702111 cites W2005588714 @default.
- W2891702111 cites W2007624075 @default.
- W2891702111 cites W2010421361 @default.
- W2891702111 cites W2015020748 @default.
- W2891702111 cites W2015933608 @default.
- W2891702111 cites W2016811754 @default.
- W2891702111 cites W2019636151 @default.
- W2891702111 cites W2020592781 @default.
- W2891702111 cites W2024264974 @default.
- W2891702111 cites W2024363942 @default.
- W2891702111 cites W2028884998 @default.
- W2891702111 cites W2029695041 @default.
- W2891702111 cites W2030099701 @default.
- W2891702111 cites W2030641075 @default.
- W2891702111 cites W2031218614 @default.
- W2891702111 cites W2032184521 @default.
- W2891702111 cites W2033189291 @default.
- W2891702111 cites W2033392009 @default.
- W2891702111 cites W2033686120 @default.
- W2891702111 cites W2034951782 @default.
- W2891702111 cites W2036755018 @default.
- W2891702111 cites W2037001270 @default.
- W2891702111 cites W203704093 @default.
- W2891702111 cites W2037450156 @default.
- W2891702111 cites W2039328251 @default.
- W2891702111 cites W2041464039 @default.
- W2891702111 cites W2041601288 @default.
- W2891702111 cites W2041948915 @default.
- W2891702111 cites W2042794149 @default.
- W2891702111 cites W2045043328 @default.
- W2891702111 cites W2045190174 @default.
- W2891702111 cites W2045855955 @default.
- W2891702111 cites W2046682365 @default.
- W2891702111 cites W2047199712 @default.
- W2891702111 cites W2051406458 @default.
- W2891702111 cites W2052742260 @default.
- W2891702111 cites W2053035647 @default.
- W2891702111 cites W2053116497 @default.
- W2891702111 cites W2054438061 @default.
- W2891702111 cites W2055937609 @default.
- W2891702111 cites W2057806011 @default.
- W2891702111 cites W2059518746 @default.
- W2891702111 cites W2060632687 @default.
- W2891702111 cites W2061123524 @default.