Plasma Aβ40 and Aβ42 and Alzheimer’s disease

Mayeux, Richard; Honig, Lawrence S.; Tang, Mingxin; Manly, Jennifer J.; Stern, Yaakov; Schupf, Nicole; Mehta, Pankaj

doi:10.1212/01.wnl.0000091890.32140.8f

Cited by 407 publications

(347 citation statements)

References 43 publications

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“…In this study, we demonstrated that OVX for 5 weeks increased Aβ 1-40 level in serum prepared from ICR female mice at 13-14 weeks old. In accordance with our finding, several clinical studies have demonstrated that plasma Aβ 1-40 level is elevated in sporadic AD (Mayeux et al, 2003;Mehta et al, 2000) and that platelets are the major contributor of peripherally generated Aβ to the plasma (Colciaghi et al, 2004). Such abnormalities in the platelet amyloid precursor protein (APP) metabolism are observed in patients with mild cognitive impairment, as well as Alzheimer's disease (Padovani et al, 2002).…”

Section: Discussionsupporting

confidence: 91%

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Fukuzaki

Takuma

Funatsu

et al. 2008

Neurochemistry International

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Ovarian hormone decline after menopause may influence cognitive performance and increase the risk for Alzheimer's disease (AD) in women. Amyloid-β peptide (Aβ) has been proposed to be the primary cause of AD. In this study, we examined whether ovariectomy (OVX) could affect the levels of cofactors Aβ-binding alcohol dehydrogenase (ABAD) and receptor for advanced glycation endproducts (RAGE), which have been reported to potentiate Aβ-mediated neuronal perturbation, in mouse hippocampus, correlating with estrogen and Aβ levels. Female ICR mice were randomly divided into ovariectomized or sham-operated groups, and biochemical analyses were carried out at 5 weeks after the operation. OVX for 5 weeks significantly decreased hippocampal 17β-estradiol level, while it tended to reduce the hormone level in serum, compared with the sham-operated control. In contrast, OVX did not affect hippocampal Aβ 1-40 level, although it significantly increased serum Aβ 1-40 level. Furthermore, we demonstrated that OVX increased hippocampal ABAD level in neurons, but not astrocytes, while it did not affect RAGE level. These findings suggest that the expression of neuronal ABAD depends on estrogen level in the hippocampus and the increase in serum Aβ and hippocampal ABAD induced by ovarian hormone decline may be associated with pre-stage of memory deficit in postmenopausal women and Aβ-mediated AD pathology.

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Section: Discussionsupporting

confidence: 91%

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Fukuzaki

Takuma

Funatsu

et al. 2008

Neurochemistry International

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“…Higher baseline levels of Ab1-42, but not Ab1-40 have been associated with increased risk of AD over a 3-4 year period in two cohorts. [47][48][49] Conversely, low baseline levels of plasma Ab1-40 at age 77 were associated with increased AD risk in men. 50 A lower plasma Ab1-42/Ab1-40 ratio was associated with increased risk for AD over a 3-year follow-up in a longitudinal study of 563 individuals.…”

Section: Plasma Ab As a Diagnostic Markermentioning

confidence: 99%

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

et al. 2008

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Currently, the 'amyloid hypothesis' is the most widely accepted explanation for the pathogenesis of Alzheimer's disease (AD). According to this hypothesis, altered metabolism of the amyloid-b (Ab) peptide is central to the pathological cascade involved in the pathogenesis of AD. Although Ab is produced by almost every cell in the body, a physiological function for the peptide has not been determined, and the pathways by which Ab leads to cognitive dysfunction and cell death are unclear. Numerous therapeutic approaches that target the production, toxicity and removal of Ab are being developed worldwide. Although therapeutic treatment for AD may be imminent, the value and effectiveness of such treatment are largely dependent on early diagnosis of the disease. This review summarizes current knowledge of Ab clearance, transport and degradation, and evaluates the use of such information in the development of diagnostic tools. The conflicting results of plasma Ab ELISAs are discussed, as are the more promising results of Ab imaging by positron emission tomography. Current knowledge of Ab-binding proteins and Ab-degrading enzymes is analysed in the context of a potential therapy for AD. Transport across the blood-brain barrier by the receptor for advanced glycation end products and efflux via the multi-ligand lipoprotein receptor LRP-1 is also reviewed. Enhancing clearance and degradation of Ab remains an attractive therapeutic strategy, and improved understanding of Ab clearance may lead to advances in diagnostics and interventions designed to prevent or delay the onset of AD.

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“…Recently it was suggested that the inflammation induced by the accumulation of Aβ is not an only a local phenomenon but can induce systemic symptoms or be caused by systemic events (Britschgi and Wyss-Coray, 2007;Richartz-Salzburger et al, 2007;Fiala et al, 2005). Moreover, it is likely that Aβ is not only accumulated in the brains of AD patients, but is also present in the periphery and can be detected in the blood (Britschgi and Wyss-Coray, 2007;Mayeux et al, 2003;Sagare et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Immune profiling of Alzheimer patients

Pellicanò

Larbi

Goldeck

et al. 2012

Journal of Neuroimmunology

127

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Alzheimer's disease (AD) is characterized by extracellular senile plaques in the brain, containing amyloid-β peptide (Aβ). We identify immunological differences between AD patients and age-matched controls greater than those related to age itself. The biggest differences were in the CD4+ rather than the CD8+ T cell compartment resulting in lower proportions of naïve cells, more late-differentiated cells and higher percentages of activated CD4+CD25+ T cells without a Treg phenotype in AD patients. Changes to CD4+ cells might be the result of chronic stimulation by Aβ present in the blood. These findings have implications for diagnosis and understanding the aetiology of the disease.

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Plasma Aβ40 and Aβ42 and Alzheimer’s disease

Cited by 407 publications

References 43 publications

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

Immune profiling of Alzheimer patients

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