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- W2770191803 abstract "We perform a large-scale meta-analysis of 51 peer-reviewed 3xTg-AD mouse publications to compare Alzheimer's disease (AD) quantitative clinical outcome measures, including amyloid-β (Aβ), total tau, and phosphorylated tau (pTau), with cognitive performance in Morris water maze (MWM) and Novel Object Recognition (NOR). High levels of Aβ (Aβ40, Aβ42) showed significant but weak trends with cognitive decline (MWM: slope = 0.336, R2 = 0.149, n = 259, p < 0.001; NOR: slope = 0.156, R2 = 0.064, n = 116, p < 0.05); only soluble Aβ or directly measured Aβ meaningfully contribute. Tau expression in 3xTg-AD mice was within 10-20% of wild type and not associated with cognitive decline. In contrast, increased pTau is directly and significantly correlated with cognitive decline in MWM (slope = 0.408, R2 = 0.275, n = 371, p < < 0.01) and NOR (slope = 0.319, R2 = 0.176, n = 113, p < 0.05). While a variety of pTau epitopes (AT8, AT270, AT180, PHF-1) were examined, AT8 correlated most strongly with cognition (slope = 0.586, R2 = 0.521, n = 185, p < < 0.001). Multiple linear regression confirmed pTau is a stronger predictor of MWM performance than Aβ. Despite pTau's lower physical concentration than Aβ, pTau levels more directly and quantitatively correlate with 3xTg-AD cognitive decline. pTau's contribution to neurofibrillary tangles well after Aβ levels plateau makes pTau a viable treatment target even in late-stage clinical AD. Principal component analysis, which included hyperphosphorylation induced by kinases (pGSK3β, GSK3β, CDK5), identified phosphorylated ser9 GSK3β as the primary contributor to MWM variance. In summary, meta-analysis of cognitive decline in preclinical AD finds tauopathy more impactful than Aβ. Nonetheless, complex AD interactions dictate successful therapeutics harness synergy between Aβ and pTau, possibly through the GSK3 pathway." @default.
- W2770191803 created "2017-12-04" @default.
- W2770191803 creator A5011455956 @default.
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- W2770191803 creator A5040777199 @default.
- W2770191803 creator A5085546848 @default.
- W2770191803 creator A5088494951 @default.
- W2770191803 date "2017-11-28" @default.
- W2770191803 modified "2023-10-03" @default.
- W2770191803 title "Cognitive Decline in Preclinical Alzheimer’s Disease: Amyloid-Beta versus Tauopathy" @default.
- W2770191803 cites W1501075116 @default.
- W2770191803 cites W1518040978 @default.
- W2770191803 cites W1520903105 @default.
- W2770191803 cites W1522698448 @default.
- W2770191803 cites W1538595291 @default.
- W2770191803 cites W1550794020 @default.
- W2770191803 cites W1562146500 @default.
- W2770191803 cites W1566600743 @default.
- W2770191803 cites W1577837690 @default.
- W2770191803 cites W1597163915 @default.
- W2770191803 cites W1640935438 @default.
- W2770191803 cites W1946583083 @default.
- W2770191803 cites W1965263019 @default.
- W2770191803 cites W1967061503 @default.
- W2770191803 cites W1967464880 @default.
- W2770191803 cites W1972165428 @default.
- W2770191803 cites W1972371732 @default.
- W2770191803 cites W1973276273 @default.
- W2770191803 cites W1973927723 @default.
- W2770191803 cites W1975015501 @default.
- W2770191803 cites W1977002082 @default.
- W2770191803 cites W1981527089 @default.
- W2770191803 cites W1984652813 @default.
- W2770191803 cites W1988011540 @default.
- W2770191803 cites W1991347149 @default.
- W2770191803 cites W1994083528 @default.
- W2770191803 cites W1994336523 @default.
- W2770191803 cites W1994580609 @default.
- W2770191803 cites W1996542389 @default.
- W2770191803 cites W1996731829 @default.
- W2770191803 cites W1997192733 @default.
- W2770191803 cites W1999009790 @default.
- W2770191803 cites W2000029832 @default.
- W2770191803 cites W2000031112 @default.
- W2770191803 cites W2001229756 @default.
- W2770191803 cites W2001870831 @default.
- W2770191803 cites W2002106007 @default.
- W2770191803 cites W2003966687 @default.
- W2770191803 cites W2005755021 @default.
- W2770191803 cites W2008980341 @default.
- W2770191803 cites W2013146608 @default.
- W2770191803 cites W2019427919 @default.
- W2770191803 cites W2022410893 @default.
- W2770191803 cites W2023041924 @default.
- W2770191803 cites W2026816538 @default.
- W2770191803 cites W2028457208 @default.
- W2770191803 cites W2029580869 @default.
- W2770191803 cites W2038804438 @default.
- W2770191803 cites W2039076728 @default.
- W2770191803 cites W2039851764 @default.
- W2770191803 cites W2040787372 @default.
- W2770191803 cites W2045007926 @default.
- W2770191803 cites W2045489211 @default.
- W2770191803 cites W2045872917 @default.
- W2770191803 cites W2051268743 @default.
- W2770191803 cites W2061419556 @default.
- W2770191803 cites W2065413916 @default.
- W2770191803 cites W2069454756 @default.
- W2770191803 cites W2069812964 @default.
- W2770191803 cites W2070270048 @default.
- W2770191803 cites W2070478570 @default.
- W2770191803 cites W2072707752 @default.
- W2770191803 cites W2075193321 @default.
- W2770191803 cites W2078523422 @default.
- W2770191803 cites W2079540265 @default.
- W2770191803 cites W2080228122 @default.
- W2770191803 cites W2082429191 @default.
- W2770191803 cites W2082905363 @default.
- W2770191803 cites W2086477221 @default.
- W2770191803 cites W2089512770 @default.
- W2770191803 cites W2089740883 @default.
- W2770191803 cites W2090349395 @default.
- W2770191803 cites W2094063510 @default.
- W2770191803 cites W2094958540 @default.
- W2770191803 cites W2096481146 @default.
- W2770191803 cites W2096963202 @default.
- W2770191803 cites W2098463163 @default.
- W2770191803 cites W2101141112 @default.
- W2770191803 cites W2103440561 @default.
- W2770191803 cites W2103716597 @default.
- W2770191803 cites W2106735088 @default.
- W2770191803 cites W2108741722 @default.
- W2770191803 cites W2112541356 @default.
- W2770191803 cites W2112896415 @default.
- W2770191803 cites W2121448546 @default.
- W2770191803 cites W2127381922 @default.
- W2770191803 cites W2129470375 @default.
- W2770191803 cites W2136466563 @default.