Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes

Vidal, Rubén; Ghiso, Jorge; Wısnıewskı, Thomas; Frangione, Blas

doi:10.1016/0014-5793(96)00845-9

Cited by 18 publications

(12 citation statements)

References 25 publications

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“…In order to show that platelets contain enzymes included in APP processing, we examined whether BACE-1 and presenilin-1 are present in platelets by means of Western blotting. We found that platelets contain BACE-1 and that presenilin-1 is present in platelets, in accordance with recent studies [23,24] (fig. 3).…”

Section: Discussionsupporting

confidence: 81%

“…Moreover, there are also studies suggesting that platelets are the general source of ·-sAPP and Aß 40 in human blood [20][21][22], thus either platelets or megakaryocytes may contain the whole repertoire of enzymes required for APP processing. Recently, presenilin-1 and presenilin-2 have been found to be expressed in the cells [23,24]. However, due to the low concentration of Aß 42 in plasma, the peripheral source of Aß 42 remains to be established.…”

Section: Introductionmentioning

confidence: 99%

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Unaltered Plasma Levels of β-Amyloid(1–40) and β-Amyloid(1–42) upon Stimulation of Human Platelets

Olsson

Vanmechelen²,

Vanderstichele³

et al. 2003

Dement Geriatr Cogn Disord

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Accumulation of β-amyloid (Aβ) in the brain is one of the central lesions in Alzheimer’s disease (AD). Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP, Aβ₄₀ and Aβ₄₂. Platelets have been regarded as the primary source of circulating APP and Aβ. Plasma levels of Aβ may therefore be dependent on platelet activation. We analysed Aβ_40/42 in plasma in the presence of physiological agonists of platelet activation such as adenosine diphosphate, collagen, thrombin, and a synthetic agonist, thrombin receptor activator peptide 6. We found that the levels of Aβ_40/42 in plasma were not related to platelet activation, suggesting that sampling techniques affecting platelet activation do not confound measurement of Aβ_40/42in plasma.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Unaltered Plasma Levels of β-Amyloid(1–40) and β-Amyloid(1–42) upon Stimulation of Human Platelets

Olsson

Vanmechelen²,

Vanderstichele³

et al. 2003

Dement Geriatr Cogn Disord

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“…In other words we demonstrate a distinction in VRSQ+ expression between brain and peripheral tissue. The PS-1 gene has several splicing variants which differ from tissue to tissue (Vidal et at., 1996;Rogaev et al, 1997). Further examination of other alternative splicing products is necessary in peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

Alteration in brain presenilin‐1 mRNA expression in sporadic Alzheimer's disease

Isoe-Wada¹,

Urakami²,

Wakutani³

et al. 1999

Euro J of Neurology

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Expression of presenilin-1 (PS-1) mRNA in an alternative splicing at the 3' end of exon 3 was examined in brain tissue, lymphocytes and cultured skin fibroblasts using the RT- polymerase chain reaction (RT-PCR) method. We quantified the relative ratios of the densities of the long form of PS-1 mRNA, which contains a sequence encoding four amino acids (VRSQ, denoted as VRSQ+) to the short form, which lacks the VRSQ sequence (VRSQ-). The brain tissue of subjects with sporadic Alzheimer's disease (AD) had reduced levels of the VRSQ+ form of the PS-1 mRNA compared to a control group. No significant differences appeared in peripheral tissues, such as lymphocytes or cultured skin fibroblasts in AD with control subjects. Changes in the alternative splicing of exon 3 may be specific to the brain and may play an important role in the pathogenesis of sporadic AD.

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“…Psen1 −/− ; Psen2 −/− DKO MEF cells were transiently co-transfected with empty pcDNA3.1 or pcDNA3.1-apoER2-ΔEX5 and pcDNA3.1-PS1 WT or L282V [identical mutation to L286V but in the context of a shorter splice variant (Vidal et al, 1996)] with Lipofectamine 2000 (Invitrogen). At 24 h after transfection, cells were washed with PBS and treated with 50 μM DAPT and/or 10 nM Reelin in serum-free medium for 16 h. Cells were then harvested with SDS lysis buffer as above.…”

Section: Methodsmentioning

confidence: 99%

Presenilin 1 mutations influence processing and trafficking of the ApoE receptor apoER2

Wang

Moerman-Herzog

Slaton

et al. 2017

Neurobiology of Aging

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Presenilin (PS)-1 is an intramembrane protease serving as the catalytic component of γ-secretase. Mutations in the PS1 gene are the most common cause of familial Alzheimer’s disease (FAD). The LDL-receptor family member apoER2 is a γ-secretase substrate that has been associated with AD in several ways, including acting as a receptor for apolipoprotein E. ApoER2 is processed by γ-secretase into a C-terminal fragment (γ-CTF) that appears to regulate gene expression. FAD PS1 mutations were tested for effects on apoER2. PS1 mutation R278I showed impaired γ-secretase activity for apoER2 in the basal state or after exposure to Reelin. PS1 M146V mutation permitted accumulation of apoER2 CTFs after Reelin treatment, while no difference was seen between wild-type (WT) and M146V in the basal state. PS1 L282V mutation, combined with the γ-secretase inhibitor DAPT, greatly reduced the cell-surface levels of apoER2 without affecting total apoER2 levels, suggesting a defect in receptor trafficking. These findings indicate that impaired processing or localization of apoER2 may contribute to the pathogenic effects of FAD mutations in PS1.

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Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes

Cited by 18 publications

References 25 publications

Unaltered Plasma Levels of β-Amyloid<sub>(1–40)</sub> and β-Amyloid<sub>(1–42)</sub> upon Stimulation of Human Platelets

Unaltered Plasma Levels of β-Amyloid<sub>(1–40)</sub> and β-Amyloid<sub>(1–42)</sub> upon Stimulation of Human Platelets

Alteration in brain presenilin‐1 mRNA expression in sporadic Alzheimer's disease

Presenilin 1 mutations influence processing and trafficking of the ApoE receptor apoER2

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