2004
DOI: 10.1073/pnas.0205689101
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Amyloid β peptide load is correlated with increased β-secretase activity in sporadic Alzheimer's disease patients

Abstract: Whether elevated ␤-secretase (BACE) activity is related to plaque formation or amyloid ␤ peptide (A␤) production in Alzheimer's disease (AD) brains remains inconclusive. Here, we report that we used sandwich enzyme-linked immunoabsorbent assay to quantitate various A␤ species in the frontal cortex of AD brains homogenized in 70% formic acid. We found that most of the A␤ species detected in rapidly autopsied brains (<3 h) with sporadic AD were A␤ 1-x and A␤ 1-42, as well as A␤x-42. To establish a linkage betwee… Show more

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Cited by 485 publications
(426 citation statements)
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References 33 publications
(69 reference statements)
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“…Soluble Aβ is higher in DS early in development and continues to rise with age [61]. The data presented in the current study extends these previous findings and shows that insoluble Aβ increases with age in DS but at older ages (>40 years) than that reported for soluble Aβ [61] and reaches significantly higher levels than in normal aging but closer to levels reported in AD [14,32]. We did not observe significant differences in the levels of insoluble Aβ in younger DS cases as compared to controls suggesting that insoluble Aβ reflects either an aging or a disease process.…”
Section: Discussionsupporting
confidence: 87%
See 1 more Smart Citation
“…Soluble Aβ is higher in DS early in development and continues to rise with age [61]. The data presented in the current study extends these previous findings and shows that insoluble Aβ increases with age in DS but at older ages (>40 years) than that reported for soluble Aβ [61] and reaches significantly higher levels than in normal aging but closer to levels reported in AD [14,32]. We did not observe significant differences in the levels of insoluble Aβ in younger DS cases as compared to controls suggesting that insoluble Aβ reflects either an aging or a disease process.…”
Section: Discussionsupporting
confidence: 87%
“…In normal aging, betasecretase activity increases [15] and correlates with increased amounts of insoluble Aβ1-40 and Aβ1-42 [15]. In AD autopsy samples, BACE protein and beta-secretase activity levels are increased relative to age-matched controls [14,32,62,69] and alpha-secretase activity is reduced [62]. However, in AD brain, beta-secretase activity does not correlate with insoluble Aβ peptide [14].…”
Section: Discussionmentioning
confidence: 97%
“…[21][22][23] However, this lack of association may be due to the multiple forms of Ab assembly, such that memory impairment and neurotoxicity may be due to soluble oligomers of Ab. Indeed, the level of soluble Ab, in particular Ab1-40, correlates with synaptic changes and disease severity in AD [24][25][26][27][28][29][30] (Table 1). Given the central role of Ab in AD pathogenesis, it is perhaps surprising and certainly frustrating that so little is understood of the nature of this peptide in biological systems, more specifically, which species of Ab is responsible for the neurotoxicity that is so rampant in AD.…”
Section: Biology Of Ab In the Brain And Peripherymentioning
confidence: 99%
“…In addition, elevations in C99 are toxic to neurons (Neve et al , 1996), correlating with symptoms of the disease (Rockenstein et al , 2005; Tamayev et al , 2012). Importantly, we note that although much of our data were obtained using FAD models and cells from FAD patients containing mutations in presenilins, alterations in γ‐secretase activity and increased levels of C99 have been detected in sporadic AD patients as well (Fukumoto et al , 2002; Yang et al , 2003; Li et al , 2004; Pera et al , 2013). …”
Section: Discussionmentioning
confidence: 96%