Imaging Biomarkers of Alzheimer Disease in Multiple Sclerosis

Burcu Zeydan; Val J. Lowe; Ross R. Reichard; Scott A. Przybelski; Timothy G. Lesnick; Christopher G. Schwarz; Matthew L. Senjem; Jeffrey L. Gunter; Joseph E. Parisi; Mary M. Machulda; Prashanthi Vemuri; Michelle M. Mielke; David S. Knopman; Ronald C. Petersen; Clifford R. Jack; Orhun H. Kantarci; Kejal Kantarci

doi:10.1002/ana.25684

Imaging Biomarkers of Alzheimer Disease in Multiple Sclerosis

Burcu Zeydan, Val J. Lowe, Ross R. Reichard, Scott A. Przybelski, Timothy G. Lesnick, Christopher G. Schwarz, Matthew L. Senjem, Jeffrey L. Gunter, Joseph E. Parisi, Mary M. Machulda, Prashanthi Vemuri, Michelle M. Mielke, David S. Knopman, Ronald C. Petersen, Clifford R. Jack, Orhun H. Kantarci, Kejal Kantarci

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

6 Scopus citations

Abstract

Objective: To investigate β-amyloid and tau depositions using Pittsburgh compound B (PiB) positron emission tomography (PET) and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients. Methods: Patients with MS (n = 16) and controls (n = 80) matched for age, sex, and APOE ε4 status from the population-based Mayo Clinic Study of Aging who underwent PiB PET imaging were studied. Of these individuals, 12 patients with MS and 60 matching controls also underwent AV1451 tau PET. Cortical PiB and AV1451 standard uptake value ratios (SUVrs) from the entire cortex and previously determined Alzheimer disease (AD) signature regions in the same population were calculated for group comparisons and testing for associations with age. Results: AD signature PiB SUVr (odds ratio [OR] [95% confidence interval (CI)] = 0.52 [0.27–0.98], p = 0.044), total cortical PiB SUVr (OR [95% CI] = 0.52 [0.28–0.99], p = 0.048), and the frequency of abnormal PiB SUVrs (OR [95% CI] = 0.10 [0.01–0.90], p = 0.040) were lower in MS than controls. Although AD-signature and total cortical AV1451 SUVrs were not different between the groups, the frequency of abnormal AV1451 SUVrs was higher (OR [95% CI] = 10.65 [1.10–103.35], p = 0.041) in MS than controls. The association of AD signature PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.14 [−0.023 to −0.006], p = 0.002). Similarly, the association of total cortical PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.13 [−0.021 to −0.005], p = 0.002). There was no difference in the association of AV1451 SUVr findings with age between the MS patients and controls. Interpretation: Although both β-amyloid and tau are biomarkers of cognitive aging and AD, cortical β-amyloid deposition was lower in MS than age-matched controls, suggesting that some aspect of MS pathobiology retards the accumulation of β-amyloid but not the accumulation of tau. ANN NEUROL 2020;87:556–567.

Original language	English (US)
Pages (from-to)	556-567
Number of pages	12
Journal	Annals of neurology
Volume	87
Issue number	4
DOIs	https://doi.org/10.1002/ana.25684
State	Published - Apr 1 2020

ASJC Scopus subject areas

Neurology
Clinical Neurology

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Zeydan, B., Lowe, V. J., Reichard, R. R., Przybelski, S. A., Lesnick, T. G., Schwarz, C. G., Senjem, M. L., Gunter, J. L., Parisi, J. E., Machulda, M. M., Vemuri, P., Mielke, M. M., Knopman, D. S., Petersen, R. C., Jack, C. R., Kantarci, O. H., & Kantarci, K. (2020). Imaging Biomarkers of Alzheimer Disease in Multiple Sclerosis. Annals of neurology, 87(4), 556-567. https://doi.org/10.1002/ana.25684

Imaging Biomarkers of Alzheimer Disease in Multiple Sclerosis. / Zeydan, Burcu; Lowe, Val J.; Reichard, Ross R.; Przybelski, Scott A.; Lesnick, Timothy G.; Schwarz, Christopher G.; Senjem, Matthew L.; Gunter, Jeffrey L.; Parisi, Joseph E.; Machulda, Mary M.; Vemuri, Prashanthi ; Mielke, Michelle M.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Kantarci, Orhun H.; Kantarci, Kejal.

In: Annals of neurology, Vol. 87, No. 4, 01.04.2020, p. 556-567.

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

Zeydan, Burcu ; Lowe, Val J. ; Reichard, Ross R. ; Przybelski, Scott A. ; Lesnick, Timothy G. ; Schwarz, Christopher G. ; Senjem, Matthew L. ; Gunter, Jeffrey L. ; Parisi, Joseph E. ; Machulda, Mary M. ; Vemuri, Prashanthi ; Mielke, Michelle M. ; Knopman, David S. ; Petersen, Ronald C. ; Jack, Clifford R. ; Kantarci, Orhun H. ; Kantarci, Kejal. / Imaging Biomarkers of Alzheimer Disease in Multiple Sclerosis. In: Annals of neurology. 2020 ; Vol. 87, No. 4. pp. 556-567.

@article{74ecbc5e50394d3d8edd156345ae155a,

title = "Imaging Biomarkers of Alzheimer Disease in Multiple Sclerosis",

abstract = "Objective: To investigate β-amyloid and tau depositions using Pittsburgh compound B (PiB) positron emission tomography (PET) and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients. Methods: Patients with MS (n = 16) and controls (n = 80) matched for age, sex, and APOE ε4 status from the population-based Mayo Clinic Study of Aging who underwent PiB PET imaging were studied. Of these individuals, 12 patients with MS and 60 matching controls also underwent AV1451 tau PET. Cortical PiB and AV1451 standard uptake value ratios (SUVrs) from the entire cortex and previously determined Alzheimer disease (AD) signature regions in the same population were calculated for group comparisons and testing for associations with age. Results: AD signature PiB SUVr (odds ratio [OR] [95% confidence interval (CI)] = 0.52 [0.27–0.98], p = 0.044), total cortical PiB SUVr (OR [95% CI] = 0.52 [0.28–0.99], p = 0.048), and the frequency of abnormal PiB SUVrs (OR [95% CI] = 0.10 [0.01–0.90], p = 0.040) were lower in MS than controls. Although AD-signature and total cortical AV1451 SUVrs were not different between the groups, the frequency of abnormal AV1451 SUVrs was higher (OR [95% CI] = 10.65 [1.10–103.35], p = 0.041) in MS than controls. The association of AD signature PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.14 [−0.023 to −0.006], p = 0.002). Similarly, the association of total cortical PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.13 [−0.021 to −0.005], p = 0.002). There was no difference in the association of AV1451 SUVr findings with age between the MS patients and controls. Interpretation: Although both β-amyloid and tau are biomarkers of cognitive aging and AD, cortical β-amyloid deposition was lower in MS than age-matched controls, suggesting that some aspect of MS pathobiology retards the accumulation of β-amyloid but not the accumulation of tau. ANN NEUROL 2020;87:556–567.",

author = "Burcu Zeydan and Lowe, {Val J.} and Reichard, {Ross R.} and Przybelski, {Scott A.} and Lesnick, {Timothy G.} and Schwarz, {Christopher G.} and Senjem, {Matthew L.} and Gunter, {Jeffrey L.} and Parisi, {Joseph E.} and Machulda, {Mary M.} and Prashanthi Vemuri and Mielke, {Michelle M.} and Knopman, {David S.} and Petersen, {Ronald C.} and Jack, {Clifford R.} and Kantarci, {Orhun H.} and Kejal Kantarci",

note = "Funding Information: This study was funded by the NIH (NIA: P50 AG016574, U01 AG006786, R01 AG011378, R01 AG041851, R01 AG034676, R01 AG040042, RF1 AG57547, RF1 AG55151, U54 AG44170; NINDS: R01 NS097495; NCRR: C06 RR018898), the Elsie and Marvin Dekelboum Family Foundation, the Schuler Foundation, the Liston Award, the GHR Foundation, the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic, and the Mayo Foundation for Medical Education and Research. The funding sources had no role in study design, collection, analysis, interpretation, or decision to submit this paper. We thank Avid Radiopharmaceuticals for their support in supplying AV-1451 precursor, chemistry production advice and oversight, and the US Food and Drug Administration regulatory cross-filing permission and documentation needed for this work.",

year = "2020",

month = apr,

day = "1",

doi = "10.1002/ana.25684",

language = "English (US)",

volume = "87",

pages = "556--567",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "4",

}

TY - JOUR

T1 - Imaging Biomarkers of Alzheimer Disease in Multiple Sclerosis

AU - Zeydan, Burcu

AU - Lowe, Val J.

AU - Reichard, Ross R.

AU - Przybelski, Scott A.

AU - Lesnick, Timothy G.

AU - Schwarz, Christopher G.

AU - Senjem, Matthew L.

AU - Gunter, Jeffrey L.

AU - Parisi, Joseph E.

AU - Machulda, Mary M.

AU - Vemuri, Prashanthi

AU - Mielke, Michelle M.

AU - Knopman, David S.

AU - Petersen, Ronald C.

AU - Jack, Clifford R.

AU - Kantarci, Orhun H.

AU - Kantarci, Kejal

N1 - Funding Information: This study was funded by the NIH (NIA: P50 AG016574, U01 AG006786, R01 AG011378, R01 AG041851, R01 AG034676, R01 AG040042, RF1 AG57547, RF1 AG55151, U54 AG44170; NINDS: R01 NS097495; NCRR: C06 RR018898), the Elsie and Marvin Dekelboum Family Foundation, the Schuler Foundation, the Liston Award, the GHR Foundation, the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic, and the Mayo Foundation for Medical Education and Research. The funding sources had no role in study design, collection, analysis, interpretation, or decision to submit this paper. We thank Avid Radiopharmaceuticals for their support in supplying AV-1451 precursor, chemistry production advice and oversight, and the US Food and Drug Administration regulatory cross-filing permission and documentation needed for this work.

PY - 2020/4/1

Y1 - 2020/4/1

N2 - Objective: To investigate β-amyloid and tau depositions using Pittsburgh compound B (PiB) positron emission tomography (PET) and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients. Methods: Patients with MS (n = 16) and controls (n = 80) matched for age, sex, and APOE ε4 status from the population-based Mayo Clinic Study of Aging who underwent PiB PET imaging were studied. Of these individuals, 12 patients with MS and 60 matching controls also underwent AV1451 tau PET. Cortical PiB and AV1451 standard uptake value ratios (SUVrs) from the entire cortex and previously determined Alzheimer disease (AD) signature regions in the same population were calculated for group comparisons and testing for associations with age. Results: AD signature PiB SUVr (odds ratio [OR] [95% confidence interval (CI)] = 0.52 [0.27–0.98], p = 0.044), total cortical PiB SUVr (OR [95% CI] = 0.52 [0.28–0.99], p = 0.048), and the frequency of abnormal PiB SUVrs (OR [95% CI] = 0.10 [0.01–0.90], p = 0.040) were lower in MS than controls. Although AD-signature and total cortical AV1451 SUVrs were not different between the groups, the frequency of abnormal AV1451 SUVrs was higher (OR [95% CI] = 10.65 [1.10–103.35], p = 0.041) in MS than controls. The association of AD signature PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.14 [−0.023 to −0.006], p = 0.002). Similarly, the association of total cortical PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.13 [−0.021 to −0.005], p = 0.002). There was no difference in the association of AV1451 SUVr findings with age between the MS patients and controls. Interpretation: Although both β-amyloid and tau are biomarkers of cognitive aging and AD, cortical β-amyloid deposition was lower in MS than age-matched controls, suggesting that some aspect of MS pathobiology retards the accumulation of β-amyloid but not the accumulation of tau. ANN NEUROL 2020;87:556–567.

AB - Objective: To investigate β-amyloid and tau depositions using Pittsburgh compound B (PiB) positron emission tomography (PET) and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients. Methods: Patients with MS (n = 16) and controls (n = 80) matched for age, sex, and APOE ε4 status from the population-based Mayo Clinic Study of Aging who underwent PiB PET imaging were studied. Of these individuals, 12 patients with MS and 60 matching controls also underwent AV1451 tau PET. Cortical PiB and AV1451 standard uptake value ratios (SUVrs) from the entire cortex and previously determined Alzheimer disease (AD) signature regions in the same population were calculated for group comparisons and testing for associations with age. Results: AD signature PiB SUVr (odds ratio [OR] [95% confidence interval (CI)] = 0.52 [0.27–0.98], p = 0.044), total cortical PiB SUVr (OR [95% CI] = 0.52 [0.28–0.99], p = 0.048), and the frequency of abnormal PiB SUVrs (OR [95% CI] = 0.10 [0.01–0.90], p = 0.040) were lower in MS than controls. Although AD-signature and total cortical AV1451 SUVrs were not different between the groups, the frequency of abnormal AV1451 SUVrs was higher (OR [95% CI] = 10.65 [1.10–103.35], p = 0.041) in MS than controls. The association of AD signature PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.14 [−0.023 to −0.006], p = 0.002). Similarly, the association of total cortical PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.13 [−0.021 to −0.005], p = 0.002). There was no difference in the association of AV1451 SUVr findings with age between the MS patients and controls. Interpretation: Although both β-amyloid and tau are biomarkers of cognitive aging and AD, cortical β-amyloid deposition was lower in MS than age-matched controls, suggesting that some aspect of MS pathobiology retards the accumulation of β-amyloid but not the accumulation of tau. ANN NEUROL 2020;87:556–567.

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