1H MR spectroscopy biomarkers of neuronal and synaptic function are associated with tau deposition in cognitively unimpaired older adults

Firat Kara; James M. Joers; Dinesh K. Deelchand; Young Woo Park; Scott A. Przybelski; Timothy G. Lesnick; Matthew L. Senjem; Burcu Zeydan; David S. Knopman; Val J. Lowe; Prashanthi Vemuri; Michelle M. Mielke; Mary M. Machulda; Clifford R. Jack; Ronald C. Petersen; Gülin Öz; Kejal Kantarci

doi:10.1016/j.neurobiolaging.2021.12.010

¹H MR spectroscopy biomarkers of neuronal and synaptic function are associated with tau deposition in cognitively unimpaired older adults

Firat Kara, James M. Joers, Dinesh K. Deelchand, Young Woo Park, Scott A. Przybelski, Timothy G. Lesnick, Matthew L. Senjem, Burcu Zeydan, David S. Knopman, Val J. Lowe, Prashanthi Vemuri, Michelle M. Mielke, Mary M. Machulda, Clifford R. Jack, Ronald C. Petersen, Gülin Öz, Kejal Kantarci

Center for Magnetic Resonance Research

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

3 Scopus citations

Abstract

Proton magnetic resonance spectroscopy (¹H MRS) may provide information on pathophysiological changes associated with tau deposition in cognitively unimpaired older adults. In this study, the associations of posterior cingulate gyrus tau and amyloid beta (Aβ) deposition on PET with ¹H MRS metabolite ratios acquired from bilateral posterior cingulate gyri were investigated in cognitively unimpaired older adults. Participants (n = 40) from the Mayo Clinic Study of Aging underwent single-voxel sLASER ¹H MRS from the posterior cingulate gyrus at 3 Tesla, ¹⁸F-flortaucipir, and ¹¹C- Pittsburgh Compound B (PiB) PET. An increase in posterior cingulate gyrus tau deposition, but not elevated Aβ, was associated with lower N-acetylaspartate/total creatine (tCr) and glutamate (Glu)/tCr ratios, and sex by tau interaction was observed in association with Glu/tCr. Higher tau levels in cognitively unimpaired older adults are associated with biomarkers of neural and synaptic injury even in the absence of cognitive impairment and these relationships appear to be stronger in women than in men.

Original language	English (US)
Pages (from-to)	16-26
Number of pages	11
Journal	Neurobiology of Aging
Volume	112
DOIs	https://doi.org/10.1016/j.neurobiolaging.2021.12.010
State	Published - Apr 2022

Bibliographical note

Funding Information:
This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Grant R01 NS080816, the NIH (U01 NS100620, P50 AG16574, C06 RR018898, R01 AG011378, R01 AG041851, U01 AG006786, R01 AG034676, R01 NS097495, P30 AG062677), The Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the Alexander Family Professorship and Katherine B. Andersen Professorship of the Mayo Clinic. The Center for Magnetic Resonance Research (CMRR) was supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) Grant P41 EB027061 and NINDS Grant P30 NS076408. We would like to greatly thank AVID Radiopharmaceuticals, Inc., for their support in supplying AV-1451 precursor, chemistry production advice, and FDA regulatory cross-filing permission and documentation needed for this work. The funding sources had no role in study design, collection, analysis, interpretation, or decision to submit this paper. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Funding Information:
This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Grant R01 NS080816 , the NIH ( U01 NS100620, P50 AG16574, C06 RR018898, R01 AG011378, R01 AG041851, U01 AG006786, R01 AG034676, R01 NS097495, P30 AG062677 ), The Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the Alexander Family Professorship and Katherine B. Andersen Professorship of the Mayo Clinic. The Center for Magnetic Resonance Research (CMRR) was supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB ) Grant P41 EB027061 and NINDS Grant P30 NS076408 . We would like to greatly thank AVID Radiopharmaceuticals, Inc., for their support in supplying AV-1451 precursor, chemistry production advice, and FDA regulatory cross-filing permission and documentation needed for this work. The funding sources had no role in study design, collection, analysis, interpretation, or decision to submit this paper. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

Amyloid-beta
Glutamate
N-acetylaspartate
Positron emission tomography
Proton magnetic resonance spectroscopy
Sex differences
Tau

Center for Magnetic Resonance Research (CMRR) tags

ANDI
SMCT
P41

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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10.1016/j.neurobiolaging.2021.12.010

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Kara, F., Joers, J. M., Deelchand, D. K., Park, Y. W., Przybelski, S. A., Lesnick, T. G., Senjem, M. L., Zeydan, B., Knopman, D. S., Lowe, V. J., Vemuri, P., Mielke, M. M., Machulda, M. M., Jack, C. R., Petersen, R. C., Öz, G., & Kantarci, K. (2022). ¹H MR spectroscopy biomarkers of neuronal and synaptic function are associated with tau deposition in cognitively unimpaired older adults. Neurobiology of Aging, 112, 16-26. https://doi.org/10.1016/j.neurobiolaging.2021.12.010

Kara, F, Joers, JM , Deelchand, DK , Park, YW, Przybelski, SA, Lesnick, TG, Senjem, ML, Zeydan, B, Knopman, DS, Lowe, VJ, Vemuri, P, Mielke, MM, Machulda, MM, Jack, CR, Petersen, RC, Öz, G & Kantarci, K 2022, '¹H MR spectroscopy biomarkers of neuronal and synaptic function are associated with tau deposition in cognitively unimpaired older adults', Neurobiology of Aging, vol. 112, pp. 16-26. https://doi.org/10.1016/j.neurobiolaging.2021.12.010

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title = "1H MR spectroscopy biomarkers of neuronal and synaptic function are associated with tau deposition in cognitively unimpaired older adults",

abstract = "Proton magnetic resonance spectroscopy (1H MRS) may provide information on pathophysiological changes associated with tau deposition in cognitively unimpaired older adults. In this study, the associations of posterior cingulate gyrus tau and amyloid beta (Aβ) deposition on PET with 1H MRS metabolite ratios acquired from bilateral posterior cingulate gyri were investigated in cognitively unimpaired older adults. Participants (n = 40) from the Mayo Clinic Study of Aging underwent single-voxel sLASER 1H MRS from the posterior cingulate gyrus at 3 Tesla, 18F-flortaucipir, and 11C- Pittsburgh Compound B (PiB) PET. An increase in posterior cingulate gyrus tau deposition, but not elevated Aβ, was associated with lower N-acetylaspartate/total creatine (tCr) and glutamate (Glu)/tCr ratios, and sex by tau interaction was observed in association with Glu/tCr. Higher tau levels in cognitively unimpaired older adults are associated with biomarkers of neural and synaptic injury even in the absence of cognitive impairment and these relationships appear to be stronger in women than in men.",

keywords = "Amyloid-beta, Glutamate, N-acetylaspartate, Positron emission tomography, Proton magnetic resonance spectroscopy, Sex differences, Tau",

author = "Firat Kara and Joers, {James M.} and Deelchand, {Dinesh K.} and Park, {Young Woo} and Przybelski, {Scott A.} and Lesnick, {Timothy G.} and Senjem, {Matthew L.} and Burcu Zeydan and Knopman, {David S.} and Lowe, {Val J.} and Prashanthi Vemuri and Mielke, {Michelle M.} and Machulda, {Mary M.} and Jack, {Clifford R.} and Petersen, {Ronald C.} and G{\"u}lin {\"O}z and Kejal Kantarci",

note = "Funding Information: This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Grant R01 NS080816, the NIH (U01 NS100620, P50 AG16574, C06 RR018898, R01 AG011378, R01 AG041851, U01 AG006786, R01 AG034676, R01 NS097495, P30 AG062677), The Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the Alexander Family Professorship and Katherine B. Andersen Professorship of the Mayo Clinic. The Center for Magnetic Resonance Research (CMRR) was supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) Grant P41 EB027061 and NINDS Grant P30 NS076408. We would like to greatly thank AVID Radiopharmaceuticals, Inc., for their support in supplying AV-1451 precursor, chemistry production advice, and FDA regulatory cross-filing permission and documentation needed for this work. The funding sources had no role in study design, collection, analysis, interpretation, or decision to submit this paper. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Grant R01 NS080816 , the NIH ( U01 NS100620, P50 AG16574, C06 RR018898, R01 AG011378, R01 AG041851, U01 AG006786, R01 AG034676, R01 NS097495, P30 AG062677 ), The Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the Alexander Family Professorship and Katherine B. Andersen Professorship of the Mayo Clinic. The Center for Magnetic Resonance Research (CMRR) was supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB ) Grant P41 EB027061 and NINDS Grant P30 NS076408 . We would like to greatly thank AVID Radiopharmaceuticals, Inc., for their support in supplying AV-1451 precursor, chemistry production advice, and FDA regulatory cross-filing permission and documentation needed for this work. The funding sources had no role in study design, collection, analysis, interpretation, or decision to submit this paper. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = apr,

doi = "10.1016/j.neurobiolaging.2021.12.010",

language = "English (US)",

volume = "112",

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journal = "Neurobiology of Aging",

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T1 - 1H MR spectroscopy biomarkers of neuronal and synaptic function are associated with tau deposition in cognitively unimpaired older adults

AU - Kara, Firat

AU - Joers, James M.

AU - Deelchand, Dinesh K.

AU - Park, Young Woo

AU - Przybelski, Scott A.

AU - Lesnick, Timothy G.

AU - Senjem, Matthew L.

AU - Zeydan, Burcu

AU - Knopman, David S.

AU - Lowe, Val J.

AU - Vemuri, Prashanthi

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AU - Machulda, Mary M.

AU - Jack, Clifford R.

AU - Petersen, Ronald C.

AU - Öz, Gülin

AU - Kantarci, Kejal

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N2 - Proton magnetic resonance spectroscopy (1H MRS) may provide information on pathophysiological changes associated with tau deposition in cognitively unimpaired older adults. In this study, the associations of posterior cingulate gyrus tau and amyloid beta (Aβ) deposition on PET with 1H MRS metabolite ratios acquired from bilateral posterior cingulate gyri were investigated in cognitively unimpaired older adults. Participants (n = 40) from the Mayo Clinic Study of Aging underwent single-voxel sLASER 1H MRS from the posterior cingulate gyrus at 3 Tesla, 18F-flortaucipir, and 11C- Pittsburgh Compound B (PiB) PET. An increase in posterior cingulate gyrus tau deposition, but not elevated Aβ, was associated with lower N-acetylaspartate/total creatine (tCr) and glutamate (Glu)/tCr ratios, and sex by tau interaction was observed in association with Glu/tCr. Higher tau levels in cognitively unimpaired older adults are associated with biomarkers of neural and synaptic injury even in the absence of cognitive impairment and these relationships appear to be stronger in women than in men.

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KW - Amyloid-beta

KW - Glutamate

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KW - Positron emission tomography

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KW - Sex differences

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