Association of Plasma Aß Peptides with Blood Pressure in the Elderly

Lambert, Jean‐Charles; Dallongeville, Jean; Ellis, Kathryn A.; Schraen, Susanna; Lui, James; Laws, Simon M.; Dumont, Julie; Richard, Florence; Cottel, Dominique; Berr, Claudine; Ames, David; Masters, Colin L.; Rowe, Christopher C.; Szoeke, Cassandra; Tzourio, Christophe; Dartigues, Jean‐François; Buée, Luc; Martins, Ralph N.; Amouyel, Philippe

doi:10.1371/journal.pone.0018536

Cited by 20 publications

(25 citation statements)

References 29 publications

(33 reference statements)

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“…This is of particular interest, as blood pressure modulation is one of the suspected physiological functions of Aβ peptides. 5,11 With importance, we confirmed the enrichment of pathway involved in the development of neurons and in neuronal functions using the Webgestalt software.…”

Section: Discussionmentioning

confidence: 54%

“…31–34 Other pathways appear to be related to potential physiological functions of APP in the brain (e.g., axonal guidance signaling; see Supplementary Material Table 6) 35,36 or directly associated with Aβ peptides’ properties, for example, blood pressure modulation (renin-angiotensin signaling). 11 As pathway analyses depend on the tool, algorithm and pathway database used, we attempted to confirm our findings using the Webgestalt software. As a result, we observed 120 gene ontology categories significantly enriched ( P <0.05 after correction) (See Table 2 for the most significant pathways).…”

Section: Resultsmentioning

confidence: 93%

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A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

et al. 2014

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Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides’ functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1–40 and Aβ1–42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10−5). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1–42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1–42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.

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Section: Discussionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 93%

A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

et al. 2014

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“…Regarding the relationship between plasma A β and lifestyle, no direct association was found with systolic or diastolic blood pressure,38, 39 nor with alcohol intake, hours of sleep or smoking amount by questionnaire survey. Physical and motor activity, including 10MWT, RDT, TUG, and WBRT as candidates for integrated cognitive processes that require attention, planning, visuospatial, and motor processes, demonstrated linear associations with the plasma A β 40/42 ratio.…”

Section: Discussionmentioning

confidence: 76%

Aging and APOE‐ε4 are determinative factors of plasma Aβ42 levels

Nakamura

Kawarabayashi

Seino

et al. 2018

Ann Clin Transl Neurol

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ObjectiveThe aim of this study was to confirm determinative factors for plasma Aβ and its association with cognitive function.MethodsFasting plasma Aβ40 and Aβ42 levels were measured by ELISA in 1019 participants in the Iwaki Health Promotion Project. The relationships between plasma Aβ and health‐related items, including physical characteristics, cognitive function tests, blood chemistry, and APOE‐ε4 genotype were analyzed.ResultsThe plasma levels of Aβ40 and Aβ42, and Aβ40/42 ratio were found to significantly increase with aging. The age‐dependent increase in Aβ42 level was significantly suppressed by APOE‐ε4. Renal function was an associated factor for the plasma Aβ40 level. The plasma Aβ42 level and Aβ40/42 ratio correlated with cognitive function.InterpretationAge and APOE‐ε4 are major determinative factors of plasma levels of Aβ42 and the Aβ40/42 ratio. These factors are critical adjustment factors for the usage of plasma Aβ as a biomarker of central nervous system amyloidosis.

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“…Plasma Aβ concentrations have also been linked to vascular brain pathology in the case of Aβ40 [21] and in longitudinal studies of plasma Aβ concentrations were related to progression to mixed and vascular dementia [28] and hypertension [29]. …”

Section: Introductionmentioning

confidence: 99%

Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI

et al. 2011

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Previous studies of Aβ plasma as a biomarker for Alzheimer’s disease (AD) obtained conflicting results. We here included 715 subjects with baseline Aβ1–40 and Aβ1–42 plasma measurement (50% with 4 serial annual measurements): 205 cognitively normal controls (CN), 348 patients mild cognitive impairment (MCI) and 162 with AD. We assessed the factors that modified their concentrations and correlated these values with PIB PET, MRI and tau and Aβ1–42 measures in cerebrospinal fluid (CSF). Association between Aβ and diagnosis (baseline and prospective) was assessed. A number of health conditions were associated with altered concentrations of plasma Aβ. The effect of age differed according to AD stage. Plasma Aβ1–42 showed mild correlation with other biomarkers of Aβ pathology and were associated with infarctions in MRI. Longitudinal measurements of Aβ1–40 and Aβ1–42 plasma levels showed modest value as a prognostic factor for clinical progression. Our longitudinal study of complementary measures of Aβ pathology (PIB, CSF and plasma Aβ) and other biomarkers in a cohort with an extensive neuropsychological battery is significant because it shows that plasma Aβ measurements have limited value for disease classification and modest value as prognostic factors over the 3-year follow-up. However, with longer follow-up, within subject plasma Aβ measurements could be used as a simple and minimally invasive screen to identify those at increased risk for AD. Our study emphasizes the need for a better understanding of the biology and dynamics of plasma Aβ as well as the need for longer term studies to determine the clinical utility of measuring plasma Aβ.

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Association of Plasma Aß Peptides with Blood Pressure in the Elderly

Cited by 20 publications

References 29 publications

A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

Aging and APOE‐ε4 are determinative factors of plasma Aβ42 levels

Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI

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