Platelet β-secretase activity is increased in Alzheimer's disease

Johnston, Janet; Liu, W.W.; Coulson, David T.R.; Todd, Stephen; Murphy, Suzanne; Brennan, Siobhain; Foy, Clare; Craig, David; Irvine, G. Brent; Passmore, Anthony Peter

doi:10.1016/j.neurobiolaging.2006.11.003

Cited by 72 publications

(67 citation statements)

References 37 publications

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“…The genetics of early onset AD support this model (Fassbender et al, 2001). The recent publication that ␤-secretase activity in platelets is increased in AD compared with controls (Zainaghi et al, 2007;Johnston et al, 2008) is consistent with the amyloidogenic pathway being "favored" in AD.…”

Section: Discussionsupporting

confidence: 59%

Blood-Borne Amyloid-β Dimer Correlates with Clinical Markers of Alzheimer's Disease

Villemagne¹,

Perez²,

Pike³

et al. 2010

J. Neurosci.

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Alzheimer's disease (AD) is the most common age-related dementia. Unfortunately due to a lack of validated biomarkers definitive diagnosis relies on the histological demonstration of amyloid-␤ (A␤) plaques and tau neurofibrillary tangles. A␤ processing is implicated in AD progression and many therapeutic strategies target various aspects of this biology. While A␤ deposition is the most prominent feature of AD, oligomeric forms of A␤ have been implicated as the toxic species inducing the neuronal dysfunction. Currently there are no methods allowing routine monitoring of levels of such species in living populations. We have used surface enhanced laser desorption ionization time of flight (SELDI-TOF) mass spectrometry incorporating antibody capture to investigate whether the cellular membranecontaining fraction of blood provides a new source of biomarkers. There are significant differences in the mass spectra profiles of AD compared with HC subjects, with significantly higher levels of A␤ monomer and dimer in the blood of AD subjects. Furthermore, levels of these species correlated with clinical markers of AD including brain A␤ burden, cognitive impairment and brain atrophy. These results indicate that fundamental biochemical events relevant to AD can be monitored in blood, and that the species detected may be useful clinical biomarkers for AD.

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Section: Discussionsupporting

confidence: 59%

Blood-Borne Amyloid-β Dimer Correlates with Clinical Markers of Alzheimer's Disease

Villemagne¹,

Perez²,

Pike³

et al. 2010

J. Neurosci.

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“…There was a higher proportion of female subjects in the healthy control group than the MCI or AD groups (Table 1) but there was no significant effect of gender on the platelet secretase activity in any of the groups when tested using Students two tailed t-Test. The patients sampled in this study had a range of MMSE score (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), indicating relative heterogeneity in terms of disease progression (Table 1).…”

Section: Resultsmentioning

confidence: 98%

Platelet Alpha- and Beta- Secretase Activities are not Significantly Affected by Dementia or Mild Cognitive Impairment in Swedish Patients

Gorham

Bark²,

Meaney³

et al. 2010

CAR

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“…Measurement of β-secretase inhibitory activity β-Secretase inhibitory activity was measured following Johnston et al (2008), using a commercially available fluorogenic substrate, MCA-EVKMDAEFK-(DNP)-NH 2 . This substrate corresponded to the wild-type APP sequence, derivatised at its N-terminus with a fluorescent 7-methoxycoumarin-4-yl acetyl (MCA) group, and on its C-terminal lysine residue with a 2,4-dinitrophenyl (DNP) group.…”

Section: Preparation Of Shrimp Waste Hydrolysates(swhs)mentioning

confidence: 99%

Shrimp (Pandalopsis dispar) waste hydrolysate as a source of novel β–secretase inhibitors

2016

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In this study, purified peptides from shrimp waste hydrolysates (SWHs) were examined for their inhibitory effects against β-secretase. During consecutive purification using a Sephadex G-25 column chromatography and high performance liquid chromatography on a C18 column, a potent β-secretase inhibitory peptide Asp-Val-Leu-PheHis (629 Da) was isolated and identified from SWH24 by Q-TOF MS/MS and the IC 50 value was determined to be 92.70 μM. The β-secretase inhibition patterns of the purified peptides were found to be competitive. Among synthesized β-secretase inhibitory peptides, Leu-Phe-His had higher β-secretase inhibitory activity than the others. The result of this study suggests that the β-secretase inhibitory peptide derived from SWH24 could be potential candidates to develop nutraceuticals and pharmaceuticals.

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Platelet β-secretase activity is increased in Alzheimer's disease

Cited by 72 publications

References 37 publications

Blood-Borne Amyloid-β Dimer Correlates with Clinical Markers of Alzheimer's Disease

Blood-Borne Amyloid-β Dimer Correlates with Clinical Markers of Alzheimer's Disease

Platelet Alpha- and Beta- Secretase Activities are not Significantly Affected by Dementia or Mild Cognitive Impairment in Swedish Patients

Shrimp (Pandalopsis dispar) waste hydrolysate as a source of novel β–secretase inhibitors

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