Cross-sectional exploration of plasma biomarkers of alzheimer’s disease in down syndrome: Early data from the longitudinal investigation for enhancing down syndrome research (life-dsr) study

James A. Hendrix; David C. Airey; Angela Britton; Anna D. Burke; George T. Capone; Ronelyn Chavez; Jacqueline Chen; Brian Chicoine; Alberto C.S. Costa; Jeffrey L. Dage; Eric Doran; Anna Esbensen; Casey L. Evans; Kelley M. Faber; Tatiana M. Foroud; Sarah Hart; Kelsey Haugen; Elizabeth Head; Suzanne Hendrix; Hampus Hillerstrom; Priya S. Kishnani; Kavita Krell; Duvia Lara Ledesma; Florence Lai; Ira Lott; Cesar Ochoa-Lubinoff; Jennifer Mason; Jessie Nicodemus-Johnson; Nicholas Kyle Proctor; Margaret B. Pulsifer; Carolyn Revta; H. Diana Rosas; Tracie C. Rosser; Stephanie Santoro; Kim Schafer; Thomas Scheidemantel; Frederick Schmitt; Brian G. Skotko; Melissa R. Stasko; Amy Talboy; Amy Torres; Kristi Wilmes; Jason Woodward; Jennifer A. Zimmer; Howard H. Feldman; William Mobley

doi:10.3390/jcm10091907

Cross-sectional exploration of plasma biomarkers of alzheimer’s disease in down syndrome: Early data from the longitudinal investigation for enhancing down syndrome research (life-dsr) study

James A. Hendrix, David C. Airey, Angela Britton, Anna D. Burke, George T. Capone, Ronelyn Chavez, Jacqueline Chen, Brian Chicoine, Alberto C.S. Costa, Jeffrey L. Dage, Eric Doran, Anna Esbensen, Casey L. Evans, Kelley M. Faber, Tatiana M. Foroud, Sarah Hart, Kelsey Haugen, Elizabeth Head, Suzanne Hendrix, Hampus HillerstromPriya S. Kishnani, Kavita Krell, Duvia Lara Ledesma, Florence Lai, Ira Lott, Cesar Ochoa-Lubinoff, Jennifer Mason, Jessie Nicodemus-Johnson, Nicholas Kyle Proctor, Margaret B. Pulsifer, Carolyn Revta, H. Diana Rosas, Tracie C. Rosser, Stephanie Santoro, Kim Schafer, Thomas Scheidemantel, Frederick Schmitt, Brian G. Skotko, Melissa R. Stasko, Amy Talboy, Amy Torres, Kristi Wilmes, Jason Woodward, Jennifer A. Zimmer, Howard H. Feldman, William Mobley

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examina-tion (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at ap-proximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

Original language	English
Article number	1907
Journal	Journal of Clinical Medicine
Volume	10
Issue number	9
DOIs	https://doi.org/10.3390/jcm10091907
State	Published - May 1 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Alzheimer’s disease
Amyloid β peptide
Blood biomarkers
Down syndrome
Glial fibrillary acidic protein
Neurofilament light chain
Phosphorylated tau protein

ASJC Scopus subject areas

Medicine (all)

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10.3390/jcm10091907

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Hendrix, J. A., Airey, D. C., Britton, A., Burke, A. D., Capone, G. T., Chavez, R., Chen, J., Chicoine, B., Costa, A. C. S., Dage, J. L., Doran, E., Esbensen, A., Evans, C. L., Faber, K. M., Foroud, T. M., Hart, S., Haugen, K., Head, E., Hendrix, S., ... Mobley, W. (2021). Cross-sectional exploration of plasma biomarkers of alzheimer’s disease in down syndrome: Early data from the longitudinal investigation for enhancing down syndrome research (life-dsr) study. Journal of Clinical Medicine, 10(9), [1907]. https://doi.org/10.3390/jcm10091907

@article{e32a5cd255da4b01a080529efbcbb36e,

title = "Cross-sectional exploration of plasma biomarkers of alzheimer{\textquoteright}s disease in down syndrome: Early data from the longitudinal investigation for enhancing down syndrome research (life-dsr) study",

abstract = "With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer{\textquoteright}s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examina-tion (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at ap-proximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.",

keywords = "Alzheimer{\textquoteright}s disease, Amyloid β peptide, Blood biomarkers, Down syndrome, Glial fibrillary acidic protein, Neurofilament light chain, Phosphorylated tau protein",

author = "Hendrix, {James A.} and Airey, {David C.} and Angela Britton and Burke, {Anna D.} and Capone, {George T.} and Ronelyn Chavez and Jacqueline Chen and Brian Chicoine and Costa, {Alberto C.S.} and Dage, {Jeffrey L.} and Eric Doran and Anna Esbensen and Evans, {Casey L.} and Faber, {Kelley M.} and Foroud, {Tatiana M.} and Sarah Hart and Kelsey Haugen and Elizabeth Head and Suzanne Hendrix and Hampus Hillerstrom and Kishnani, {Priya S.} and Kavita Krell and Ledesma, {Duvia Lara} and Florence Lai and Ira Lott and Cesar Ochoa-Lubinoff and Jennifer Mason and Jessie Nicodemus-Johnson and Proctor, {Nicholas Kyle} and Pulsifer, {Margaret B.} and Carolyn Revta and Rosas, {H. Diana} and Rosser, {Tracie C.} and Stephanie Santoro and Kim Schafer and Thomas Scheidemantel and Frederick Schmitt and Skotko, {Brian G.} and Stasko, {Melissa R.} and Amy Talboy and Amy Torres and Kristi Wilmes and Jason Woodward and Zimmer, {Jennifer A.} and Feldman, {Howard H.} and William Mobley",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = may,

day = "1",

doi = "10.3390/jcm10091907",

language = "English",

volume = "10",

number = "9",

}

Hendrix, JA, Airey, DC, Britton, A, Burke, AD, Capone, GT, Chavez, R, Chen, J, Chicoine, B, Costa, ACS, Dage, JL, Doran, E, Esbensen, A, Evans, CL, Faber, KM, Foroud, TM, Hart, S, Haugen, K, Head, E, Hendrix, S, Hillerstrom, H, Kishnani, PS, Krell, K, Ledesma, DL, Lai, F, Lott, I, Ochoa-Lubinoff, C, Mason, J, Nicodemus-Johnson, J, Proctor, NK, Pulsifer, MB, Revta, C, Rosas, HD, Rosser, TC, Santoro, S, Schafer, K, Scheidemantel, T, Schmitt, F, Skotko, BG, Stasko, MR, Talboy, A, Torres, A, Wilmes, K, Woodward, J, Zimmer, JA, Feldman, HH & Mobley, W 2021, 'Cross-sectional exploration of plasma biomarkers of alzheimer’s disease in down syndrome: Early data from the longitudinal investigation for enhancing down syndrome research (life-dsr) study', Journal of Clinical Medicine, vol. 10, no. 9, 1907. https://doi.org/10.3390/jcm10091907

Cross-sectional exploration of plasma biomarkers of alzheimer’s disease in down syndrome : Early data from the longitudinal investigation for enhancing down syndrome research (life-dsr) study. / Hendrix, James A.; Airey, David C.; Britton, Angela et al.

In: Journal of Clinical Medicine, Vol. 10, No. 9, 1907, 01.05.2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Cross-sectional exploration of plasma biomarkers of alzheimer’s disease in down syndrome

T2 - Early data from the longitudinal investigation for enhancing down syndrome research (life-dsr) study

AU - Hendrix, James A.

AU - Airey, David C.

AU - Britton, Angela

AU - Burke, Anna D.

AU - Capone, George T.

AU - Chavez, Ronelyn

AU - Chen, Jacqueline

AU - Chicoine, Brian

AU - Costa, Alberto C.S.

AU - Dage, Jeffrey L.

AU - Doran, Eric

AU - Esbensen, Anna

AU - Evans, Casey L.

AU - Faber, Kelley M.

AU - Foroud, Tatiana M.

AU - Hart, Sarah

AU - Haugen, Kelsey

AU - Head, Elizabeth

AU - Hendrix, Suzanne

AU - Hillerstrom, Hampus

AU - Kishnani, Priya S.

AU - Krell, Kavita

AU - Ledesma, Duvia Lara

AU - Lai, Florence

AU - Lott, Ira

AU - Ochoa-Lubinoff, Cesar

AU - Mason, Jennifer

AU - Nicodemus-Johnson, Jessie

AU - Proctor, Nicholas Kyle

AU - Pulsifer, Margaret B.

AU - Revta, Carolyn

AU - Rosas, H. Diana

AU - Rosser, Tracie C.

AU - Santoro, Stephanie

AU - Schafer, Kim

AU - Scheidemantel, Thomas

AU - Schmitt, Frederick

AU - Skotko, Brian G.

AU - Stasko, Melissa R.

AU - Talboy, Amy

AU - Torres, Amy

AU - Wilmes, Kristi

AU - Woodward, Jason

AU - Zimmer, Jennifer A.

AU - Feldman, Howard H.

AU - Mobley, William

PY - 2021/5/1

Y1 - 2021/5/1

N2 - With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examina-tion (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at ap-proximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

AB - With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examina-tion (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at ap-proximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

KW - Alzheimer’s disease

KW - Amyloid β peptide

KW - Blood biomarkers

KW - Down syndrome

KW - Glial fibrillary acidic protein

KW - Neurofilament light chain

KW - Phosphorylated tau protein

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UR - http://www.scopus.com/inward/citedby.url?scp=85113191812&partnerID=8YFLogxK

U2 - 10.3390/jcm10091907

DO - 10.3390/jcm10091907

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AN - SCOPUS:85113191812

VL - 10

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M1 - 1907

ER -

Cross-sectional exploration of plasma biomarkers of alzheimer’s disease in down syndrome: Early data from the longitudinal investigation for enhancing down syndrome research (life-dsr) study

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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