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

Gorham, Paul R.; Bark, Natalie; Meaney, Steve; Björkhem, Ingemar; Crisby, Milita

doi:10.2174/156720510790691254

Cited by 11 publications

(5 citation statements)

References 33 publications

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“…In addition to the different β-secretase assay employed, we included greater numbers of MCI participants ( n = 97) and controls ( n = 85) in the present study, as compared to the previous one (52 MCI and 75 controls), and they were all characterized much more thoroughly from a neuropsychological perspective. One previous study also reported that platelet β-secretase activity was not elevated in MCI [ 16 ]. However, only 6 MCI participants were assessed in this study, alongside 30 healthy controls and 20 participants with probable AD.…”

Section: Discussionmentioning

confidence: 99%

“…We identified a significant 17% increase in platelet membrane β-secretase activity in AD, which did not correlate with Mini-Mental State Examination (MMSE) score, indicating that this increase did not occur as a secondary result of the disease process and may have preceded symptom onset [ 14 ]. Our small pilot study also found 24% more platelet membrane β-secretase activity in patients with MCI, as compared to controls [ 15 ], while an independent study of a smaller Swedish cohort using different assays found no significant differences in platelet α - or β-secretase activity in control, MCI, and AD groups [ 16 ]. Membrane β-secretase activity was found to be influenced by membrane cholesterol levels [ 17–18 ].…”

Section: Introductionmentioning

confidence: 85%

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Platelet Membrane β-Secretase Activity in Mild Cognitive Impairment and Conversion to Dementia: a Longitudinal Study

Fuchs¹,

Barrett

Passmore

et al. 2016

JAD

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A blood-based biomarker to complement the clinical and neuropsychological assessments used to evaluate the risk of individuals with mild cognitive impairment (MCI) developing Alzheimer’s disease (AD) would be invaluable. Previous pilot studies by our group identified elevated platelet membrane β-secretase activity in patients with AD and MCI, as compared to controls, and this activity was influenced by membrane cholesterol levels. The present study investigated baseline platelet membrane β-secretase activity and cholesterol levels in 97 MCI participants and 85 controls and explored whether these parameters differed in individuals with stable MCI, as compared to those who subsequently developed AD. To evaluate signal specificity, β-secretase activity assays were conducted in the presence and absence of beta-site amyloid-β protein precursor-cleaving enzyme (BACE) inhibitors. Baseline platelet membrane β-secretase activity did not differ significantly in MCI participants, as compared to controls, and platelet membrane cholesterol levels were significantly lower in the MCI group. The longitudinal study indicated that the activities inhibited by two different BACE inhibitors did not predict conversion to AD; however, the activity that was not affected by BACE inhibitors was significantly (40%) higher in individuals with stable MCI, as compared with those who subsequently developed AD. These findings indicated that further research into the source of this activity could contribute to a measure facilitating prediction of the risk of conversion from MCI to AD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 85%

Platelet Membrane β-Secretase Activity in Mild Cognitive Impairment and Conversion to Dementia: a Longitudinal Study

Fuchs¹,

Barrett

Passmore

et al. 2016

JAD

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“…Conflicting results are shown by these authors, suggesting that ADAM10 expression varies by tissue, disease stage and according to the study. In peripheral blood, although protein levels of ADAM10 are reduced (Colciaghi et al, 2002;Tang et al, 2006) its activity is unaltered in both MCI and AD (Gorham et al, 2010). In CNS tissue, ADAM10 gene and protein expression appear to be reduced, as well as its activity (Bernstein et al, 2003;Marcinkiewicz & Seidah, 2000;Tyler et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

ADAM10 gene expression in the blood cells of Alzheimer's disease patients and mild cognitive impairment subjects

et al. 2015

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ADAM10 is a potential biomarker for Alzheimer's disease (AD). ADAM10 protein levels are reduced in platelets of AD patients. The aim was to verify the total blood and platelet ADAM10 gene expression in AD patients and to compare with mild cognitive impairment (MCI) and healthy subjects. No significant differences in ADAM10 gene expression were observed. Therefore, the decrease of ADAM10 protein in platelets of AD patients is not caused by a reduction in ADAM10 mRNA. Further studies must be performed to investigate other pathways in the down regulation of ADAM10 protein.

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“…In an MCI group, platelet membrane β ‐secretase activity was increased by 24% compared with controls, although sensitivity (65%) and specificity (63%) were suboptimal for use as a diagnostic biomarker (Liu et al , ). An independent study of a smaller Swedish cohort found no significant differences in platelet α ‐secretase or β ‐secretase activity between control, MCI and AD groups (Gorham et al , ). Further investigation of platelet β ‐secretase activity is therefore warranted.…”

Section: Plasma and Platelet Biomarkersmentioning

confidence: 98%

The development of effective biomarkers for Alzheimer's disease: a review

Henry

Passmore

Todd

et al. 2012

Int J Geriat Psychiatry

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

Cited by 11 publications

References 33 publications

Platelet Membrane β-Secretase Activity in Mild Cognitive Impairment and Conversion to Dementia: a Longitudinal Study

Platelet Membrane β-Secretase Activity in Mild Cognitive Impairment and Conversion to Dementia: a Longitudinal Study

ADAM10 gene expression in the blood cells of Alzheimer's disease patients and mild cognitive impairment subjects

The development of effective biomarkers for Alzheimer's disease: a review

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