Association of Plasma Amylin Concentration With Alzheimer Disease and Brain Structure in Older Adults

Haihao Zhu, Qiushan Tao, Ting Fang Alvin Ang, Joseph Massaro, Qini Gan, Saraf Salim, Rui Ying Zhu, Vijaya B. Kolachalama, Xiaoling Zhang, Sheral Devine, Sanford H. Auerbach, Charles DeCarli, Rhoda Au, Wei Qiao Qiu

Research output: Contribution to journalArticle

Abstract

Importance: Preclinical studies suggest that amylin has a U-shaped dose-response association with risk of Alzheimer disease (AD). The association of plasma amylin with AD in humans is unknown. Objectives: To measure amylin concentration in plasma by using enzyme-linked immunosorbent assay and to study the association between plasma amylin, incidence of AD, and brain structure in humans. Design, Setting, and Participants: This cohort study used data from the Framingham Heart Study offspring cohort from 1998 to 2015. Using a Monte Carlo approach, participants were divided into 3 plasma amylin concentration groups: (1) low (<75 pmol/L), (2) high (75-2800 pmol/L), and (3) extremely high (≥2800 pmol/L). Data analyses were conducted October 5, 2017, to December 18, 2018. Exposures: Baseline plasma amylin concentrations at examination 7. Main Outcomes and Measures: Incidence of dementia or AD and brain volumetric measures from structural magnetic resonance imaging data. Results: From the Framingham Heart Study offspring cohort, 3061 participants (mean [SD] age at baseline, 61.0 [9.5] years; 1653 [54.0%] women) who had plasma amylin measurements, dementia incidence, and brain volume measurements on record were included in this study. The distribution of plasma amylin concentrations was highly skewed (median [interquartile range], 7.5 [4.6-18.9] pmol/L; mean [SD], 302.3 [1941.0] pmol/L; range, 0.03-44 623.7 pmol/L). Compared with the low plasma amylin concentration group, the high plasma amylin concentration group had a lower rate of AD incidence (2.3% vs 5.6%; P = .04), but the extremely high plasma amylin concentration group had a higher rate of AD incidence (14.3%; P < .001). After adjusting for age, sex, education, body mass index, diabetes, cardiovascular disease, high-density lipoprotein level, and APOE4, high plasma amylin was not associated with decreased AD risk (hazard ratio, 0.42 [95% CI, 0.16-1.14]; P = .09) but was positively associated with volume of gray matter in the temporal lobe (β = 0.17 [SE, 0.05]; P < .001). In contrast, extremely high plasma amylin concentration was associated with a higher AD risk (hazard ratio, 2.51 [95% CI, 1.38-4.57]; P = .003) but not associated with temporal lobe volume (β = 0.02 [SE, 0.07]; P = .82). Conclusions and Relevance: This study found that plasma amylin concentration was associated with AD incidence and brain structure with a U-shaped pattern. These findings are consistent with preclinical findings that suggest amylin is a neuropeptide that is physiological; however, at extremely high concentrations, it may lead to amylin aggregation and therefore may be a risk factor for AD.

Original languageEnglish (US)
Pages (from-to)e199826
JournalJAMA Network Open
Volume2
Issue number8
DOIs
StatePublished - Aug 2 2019

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Islet Amyloid Polypeptide
Alzheimer Disease
Brain
Incidence
Cohort Studies
Temporal Lobe
Dementia
Odds Ratio
Sex Education

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Association of Plasma Amylin Concentration With Alzheimer Disease and Brain Structure in Older Adults. / Zhu, Haihao; Tao, Qiushan; Ang, Ting Fang Alvin; Massaro, Joseph; Gan, Qini; Salim, Saraf; Zhu, Rui Ying; Kolachalama, Vijaya B.; Zhang, Xiaoling; Devine, Sheral; Auerbach, Sanford H.; DeCarli, Charles; Au, Rhoda; Qiu, Wei Qiao.

In: JAMA Network Open, Vol. 2, No. 8, 02.08.2019, p. e199826.

Research output: Contribution to journalArticle

Zhu, H, Tao, Q, Ang, TFA, Massaro, J, Gan, Q, Salim, S, Zhu, RY, Kolachalama, VB, Zhang, X, Devine, S, Auerbach, SH, DeCarli, C, Au, R & Qiu, WQ 2019, 'Association of Plasma Amylin Concentration With Alzheimer Disease and Brain Structure in Older Adults', JAMA Network Open, vol. 2, no. 8, pp. e199826. https://doi.org/10.1001/jamanetworkopen.2019.9826
Zhu, Haihao ; Tao, Qiushan ; Ang, Ting Fang Alvin ; Massaro, Joseph ; Gan, Qini ; Salim, Saraf ; Zhu, Rui Ying ; Kolachalama, Vijaya B. ; Zhang, Xiaoling ; Devine, Sheral ; Auerbach, Sanford H. ; DeCarli, Charles ; Au, Rhoda ; Qiu, Wei Qiao. / Association of Plasma Amylin Concentration With Alzheimer Disease and Brain Structure in Older Adults. In: JAMA Network Open. 2019 ; Vol. 2, No. 8. pp. e199826.
@article{9820111a1fd44ce8b45532bab62b750b,
title = "Association of Plasma Amylin Concentration With Alzheimer Disease and Brain Structure in Older Adults",
abstract = "Importance: Preclinical studies suggest that amylin has a U-shaped dose-response association with risk of Alzheimer disease (AD). The association of plasma amylin with AD in humans is unknown. Objectives: To measure amylin concentration in plasma by using enzyme-linked immunosorbent assay and to study the association between plasma amylin, incidence of AD, and brain structure in humans. Design, Setting, and Participants: This cohort study used data from the Framingham Heart Study offspring cohort from 1998 to 2015. Using a Monte Carlo approach, participants were divided into 3 plasma amylin concentration groups: (1) low (<75 pmol/L), (2) high (75-2800 pmol/L), and (3) extremely high (≥2800 pmol/L). Data analyses were conducted October 5, 2017, to December 18, 2018. Exposures: Baseline plasma amylin concentrations at examination 7. Main Outcomes and Measures: Incidence of dementia or AD and brain volumetric measures from structural magnetic resonance imaging data. Results: From the Framingham Heart Study offspring cohort, 3061 participants (mean [SD] age at baseline, 61.0 [9.5] years; 1653 [54.0{\%}] women) who had plasma amylin measurements, dementia incidence, and brain volume measurements on record were included in this study. The distribution of plasma amylin concentrations was highly skewed (median [interquartile range], 7.5 [4.6-18.9] pmol/L; mean [SD], 302.3 [1941.0] pmol/L; range, 0.03-44 623.7 pmol/L). Compared with the low plasma amylin concentration group, the high plasma amylin concentration group had a lower rate of AD incidence (2.3{\%} vs 5.6{\%}; P = .04), but the extremely high plasma amylin concentration group had a higher rate of AD incidence (14.3{\%}; P < .001). After adjusting for age, sex, education, body mass index, diabetes, cardiovascular disease, high-density lipoprotein level, and APOE4, high plasma amylin was not associated with decreased AD risk (hazard ratio, 0.42 [95{\%} CI, 0.16-1.14]; P = .09) but was positively associated with volume of gray matter in the temporal lobe (β = 0.17 [SE, 0.05]; P < .001). In contrast, extremely high plasma amylin concentration was associated with a higher AD risk (hazard ratio, 2.51 [95{\%} CI, 1.38-4.57]; P = .003) but not associated with temporal lobe volume (β = 0.02 [SE, 0.07]; P = .82). Conclusions and Relevance: This study found that plasma amylin concentration was associated with AD incidence and brain structure with a U-shaped pattern. These findings are consistent with preclinical findings that suggest amylin is a neuropeptide that is physiological; however, at extremely high concentrations, it may lead to amylin aggregation and therefore may be a risk factor for AD.",
author = "Haihao Zhu and Qiushan Tao and Ang, {Ting Fang Alvin} and Joseph Massaro and Qini Gan and Saraf Salim and Zhu, {Rui Ying} and Kolachalama, {Vijaya B.} and Xiaoling Zhang and Sheral Devine and Auerbach, {Sanford H.} and Charles DeCarli and Rhoda Au and Qiu, {Wei Qiao}",
year = "2019",
month = "8",
day = "2",
doi = "10.1001/jamanetworkopen.2019.9826",
language = "English (US)",
volume = "2",
pages = "e199826",
journal = "JAMA network open",
issn = "2574-3805",
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}

TY - JOUR

T1 - Association of Plasma Amylin Concentration With Alzheimer Disease and Brain Structure in Older Adults

AU - Zhu, Haihao

AU - Tao, Qiushan

AU - Ang, Ting Fang Alvin

AU - Massaro, Joseph

AU - Gan, Qini

AU - Salim, Saraf

AU - Zhu, Rui Ying

AU - Kolachalama, Vijaya B.

AU - Zhang, Xiaoling

AU - Devine, Sheral

AU - Auerbach, Sanford H.

AU - DeCarli, Charles

AU - Au, Rhoda

AU - Qiu, Wei Qiao

PY - 2019/8/2

Y1 - 2019/8/2

N2 - Importance: Preclinical studies suggest that amylin has a U-shaped dose-response association with risk of Alzheimer disease (AD). The association of plasma amylin with AD in humans is unknown. Objectives: To measure amylin concentration in plasma by using enzyme-linked immunosorbent assay and to study the association between plasma amylin, incidence of AD, and brain structure in humans. Design, Setting, and Participants: This cohort study used data from the Framingham Heart Study offspring cohort from 1998 to 2015. Using a Monte Carlo approach, participants were divided into 3 plasma amylin concentration groups: (1) low (<75 pmol/L), (2) high (75-2800 pmol/L), and (3) extremely high (≥2800 pmol/L). Data analyses were conducted October 5, 2017, to December 18, 2018. Exposures: Baseline plasma amylin concentrations at examination 7. Main Outcomes and Measures: Incidence of dementia or AD and brain volumetric measures from structural magnetic resonance imaging data. Results: From the Framingham Heart Study offspring cohort, 3061 participants (mean [SD] age at baseline, 61.0 [9.5] years; 1653 [54.0%] women) who had plasma amylin measurements, dementia incidence, and brain volume measurements on record were included in this study. The distribution of plasma amylin concentrations was highly skewed (median [interquartile range], 7.5 [4.6-18.9] pmol/L; mean [SD], 302.3 [1941.0] pmol/L; range, 0.03-44 623.7 pmol/L). Compared with the low plasma amylin concentration group, the high plasma amylin concentration group had a lower rate of AD incidence (2.3% vs 5.6%; P = .04), but the extremely high plasma amylin concentration group had a higher rate of AD incidence (14.3%; P < .001). After adjusting for age, sex, education, body mass index, diabetes, cardiovascular disease, high-density lipoprotein level, and APOE4, high plasma amylin was not associated with decreased AD risk (hazard ratio, 0.42 [95% CI, 0.16-1.14]; P = .09) but was positively associated with volume of gray matter in the temporal lobe (β = 0.17 [SE, 0.05]; P < .001). In contrast, extremely high plasma amylin concentration was associated with a higher AD risk (hazard ratio, 2.51 [95% CI, 1.38-4.57]; P = .003) but not associated with temporal lobe volume (β = 0.02 [SE, 0.07]; P = .82). Conclusions and Relevance: This study found that plasma amylin concentration was associated with AD incidence and brain structure with a U-shaped pattern. These findings are consistent with preclinical findings that suggest amylin is a neuropeptide that is physiological; however, at extremely high concentrations, it may lead to amylin aggregation and therefore may be a risk factor for AD.

AB - Importance: Preclinical studies suggest that amylin has a U-shaped dose-response association with risk of Alzheimer disease (AD). The association of plasma amylin with AD in humans is unknown. Objectives: To measure amylin concentration in plasma by using enzyme-linked immunosorbent assay and to study the association between plasma amylin, incidence of AD, and brain structure in humans. Design, Setting, and Participants: This cohort study used data from the Framingham Heart Study offspring cohort from 1998 to 2015. Using a Monte Carlo approach, participants were divided into 3 plasma amylin concentration groups: (1) low (<75 pmol/L), (2) high (75-2800 pmol/L), and (3) extremely high (≥2800 pmol/L). Data analyses were conducted October 5, 2017, to December 18, 2018. Exposures: Baseline plasma amylin concentrations at examination 7. Main Outcomes and Measures: Incidence of dementia or AD and brain volumetric measures from structural magnetic resonance imaging data. Results: From the Framingham Heart Study offspring cohort, 3061 participants (mean [SD] age at baseline, 61.0 [9.5] years; 1653 [54.0%] women) who had plasma amylin measurements, dementia incidence, and brain volume measurements on record were included in this study. The distribution of plasma amylin concentrations was highly skewed (median [interquartile range], 7.5 [4.6-18.9] pmol/L; mean [SD], 302.3 [1941.0] pmol/L; range, 0.03-44 623.7 pmol/L). Compared with the low plasma amylin concentration group, the high plasma amylin concentration group had a lower rate of AD incidence (2.3% vs 5.6%; P = .04), but the extremely high plasma amylin concentration group had a higher rate of AD incidence (14.3%; P < .001). After adjusting for age, sex, education, body mass index, diabetes, cardiovascular disease, high-density lipoprotein level, and APOE4, high plasma amylin was not associated with decreased AD risk (hazard ratio, 0.42 [95% CI, 0.16-1.14]; P = .09) but was positively associated with volume of gray matter in the temporal lobe (β = 0.17 [SE, 0.05]; P < .001). In contrast, extremely high plasma amylin concentration was associated with a higher AD risk (hazard ratio, 2.51 [95% CI, 1.38-4.57]; P = .003) but not associated with temporal lobe volume (β = 0.02 [SE, 0.07]; P = .82). Conclusions and Relevance: This study found that plasma amylin concentration was associated with AD incidence and brain structure with a U-shaped pattern. These findings are consistent with preclinical findings that suggest amylin is a neuropeptide that is physiological; however, at extremely high concentrations, it may lead to amylin aggregation and therefore may be a risk factor for AD.

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