FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1964117773> ?p ?o ?g. }

• W1964117773 endingPage "34" @default.
• W1964117773 startingPage "25" @default.
• W1964117773 abstract "Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-β (Aβ) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between Aβ and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence of Aβ accumulation in late-onset AD." @default.
• W1964117773 created "2016-06-24" @default.
• W1964117773 creator A5074219521 @default.
• W1964117773 creator A5083802134 @default.
• W1964117773 date "2012-11-27" @default.
• W1964117773 modified "2023-10-14" @default.
• W1964117773 title "Deciphering the mechanism underlying late-onset Alzheimer disease" @default.
• W1964117773 cites W1488124756 @default.
• W1964117773 cites W1527636392 @default.
• W1964117773 cites W1540420763 @default.
• W1964117773 cites W1575120918 @default.
• W1964117773 cites W1594033512 @default.
• W1964117773 cites W1622777525 @default.
• W1964117773 cites W1785214340 @default.
• W1964117773 cites W1916743150 @default.
• W1964117773 cites W1919353 @default.
• W1964117773 cites W1966483086 @default.
• W1964117773 cites W1968553823 @default.
• W1964117773 cites W1973573196 @default.
• W1964117773 cites W1977585036 @default.
• W1964117773 cites W1978116973 @default.
• W1964117773 cites W1979369962 @default.
• W1964117773 cites W1981715127 @default.
• W1964117773 cites W1985438873 @default.
• W1964117773 cites W1987011447 @default.
• W1964117773 cites W1991282216 @default.
• W1964117773 cites W1993023011 @default.
• W1964117773 cites W1993305977 @default.
• W1964117773 cites W1994394172 @default.
• W1964117773 cites W1994539511 @default.
• W1964117773 cites W1996153970 @default.
• W1964117773 cites W2000983899 @default.
• W1964117773 cites W2001410029 @default.
• W1964117773 cites W2002226709 @default.
• W1964117773 cites W2003525136 @default.
• W1964117773 cites W2006035554 @default.
• W1964117773 cites W2007638129 @default.
• W1964117773 cites W2009102898 @default.
• W1964117773 cites W2010464023 @default.
• W1964117773 cites W2014886338 @default.
• W1964117773 cites W2014911084 @default.
• W1964117773 cites W2015759485 @default.
• W1964117773 cites W2016913897 @default.
• W1964117773 cites W2018054225 @default.
• W1964117773 cites W2020194826 @default.
• W1964117773 cites W2021652661 @default.
• W1964117773 cites W2023136593 @default.
• W1964117773 cites W2027042725 @default.
• W1964117773 cites W2027080434 @default.
• W1964117773 cites W2029300652 @default.
• W1964117773 cites W2032190992 @default.
• W1964117773 cites W2033987011 @default.
• W1964117773 cites W2036362108 @default.
• W1964117773 cites W2036893756 @default.
• W1964117773 cites W2037099926 @default.
• W1964117773 cites W2037677220 @default.
• W1964117773 cites W2038532164 @default.
• W1964117773 cites W2038594716 @default.
• W1964117773 cites W2041546150 @default.
• W1964117773 cites W2041812587 @default.
• W1964117773 cites W2045637037 @default.
• W1964117773 cites W2047364115 @default.
• W1964117773 cites W2048584554 @default.
• W1964117773 cites W2049695088 @default.
• W1964117773 cites W2050699830 @default.
• W1964117773 cites W2051776695 @default.
• W1964117773 cites W2052794108 @default.
• W1964117773 cites W2056313099 @default.
• W1964117773 cites W2057013121 @default.
• W1964117773 cites W2059089835 @default.
• W1964117773 cites W2059189380 @default.
• W1964117773 cites W2063097902 @default.
• W1964117773 cites W2066165659 @default.
• W1964117773 cites W2066714452 @default.
• W1964117773 cites W2067854525 @default.
• W1964117773 cites W2068011527 @default.
• W1964117773 cites W2068477037 @default.
• W1964117773 cites W2072210142 @default.
• W1964117773 cites W2073868632 @default.
• W1964117773 cites W2074466908 @default.
• W1964117773 cites W2075421841 @default.
• W1964117773 cites W2077478550 @default.
• W1964117773 cites W2078941062 @default.
• W1964117773 cites W2082438248 @default.
• W1964117773 cites W2085558085 @default.
• W1964117773 cites W2086814010 @default.
• W1964117773 cites W2087685632 @default.
• W1964117773 cites W2089406620 @default.
• W1964117773 cites W2089936534 @default.
• W1964117773 cites W2091874081 @default.
• W1964117773 cites W2092176884 @default.
• W1964117773 cites W2093098435 @default.
• W1964117773 cites W2094490379 @default.
• W1964117773 cites W2095847999 @default.
• W1964117773 cites W2096158347 @default.
• W1964117773 cites W2096963202 @default.
• W1964117773 cites W2100026237 @default.
• W1964117773 cites W2102408672 @default.

• next