Early Alzheimer’s disease neuropathology detected by proton MR spectroscopy

Melissa E Murray, Scott A. Przybelski, Timothy G. Lesnick, Amanda M. Liesinger, Anthony Spychalla, Bing Zhang, Jeffrey L. Gunter, Joseph E Parisi, Bradley F Boeve, David S Knopman, Ronald Carl Petersen, Clifford R Jr. Jack, Dennis W Dickson, Kejal M Kantarci

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Proton magnetic resonance spectroscopy (1H-MRS)is sensitive to early neurodegenerative processes associated with Alzheimer’s disease (AD). Although1H-MRS metabolite ratios of N-acetyl aspartate (NAA)/creatine (Cr), NAA/myoinositol (mI), and mI/Cr measured in the posterior cingulate gyrus reveal evidence of disease progression in AD, pathologic underpinnings of the1H-MRS metabolite changes in AD are unknown. Pathologically diagnosed human cases ranging from no likelihood to high likelihood AD (n=41, 16 females and 25 males) who underwent antemortem1H-MRSof the posterior cingulate gyrus at 3 tesla were included in this study. Immunohistochemical evaluation was performed on the posterior cingulate gyrus using antibodies to synaptic vesicles, hyperphosphorylated tau (pTau), neurofibrillary tangle conformational-epitope (cNFT), amyloid-b, astrocytes, and microglia. The slides were digitally analyzed using Aperio software, which allows neuropathologic quantification in the posterior cingulate gray matter. MRS and pathology associations were adjusted for time from scan to death. Significant associations across AD and control subjects were found between reduced synaptic immunoreactivity and both NAA/Cr andNAA/mIin the posterior cingulate gyrus. Higher pTau burden was associated with lower NAA/Cr and NAA/mI. Higher amyloid-b burden was associated with elevated mI/Cr and lower NAA/mI ratios, but not with NAA/Cr.1H-MRS metabolite levels reveal early neurodegenerative changes associated with AD pathology. Our findings support the hypothesis that a decrease in NAA/Cr is associated with loss of synapses and early pTau pathology, but not with amyloid-b or later accumulation of cNFT pathology in the posterior cingulate gyrus. In addition, elevation of mI/Cr is associated with the occurrence of amyloid-b plaques in AD.

Original languageEnglish (US)
Pages (from-to)16247-16255
Number of pages9
JournalJournal of Neuroscience
Volume34
Issue number49
DOIs
StatePublished - Dec 3 2014

Fingerprint

Creatine
Protons
Gyrus Cinguli
Alzheimer Disease
Inositol
Magnetic Resonance Spectroscopy
Amyloid
Pathology
Epitopes
Neurofibrillary Tangles
Neuropathology
N-acetylaspartate
Synaptic Vesicles
Amyloid Plaques
Microglia
Astrocytes
Synapses
Disease Progression
Software
Antibodies

Keywords

  • Alzheimer’s disease
  • Digital microscopy
  • Magnetic resonance spectroscopy
  • Neuropathology
  • Posterior cingulate
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Early Alzheimer’s disease neuropathology detected by proton MR spectroscopy. / Murray, Melissa E; Przybelski, Scott A.; Lesnick, Timothy G.; Liesinger, Amanda M.; Spychalla, Anthony; Zhang, Bing; Gunter, Jeffrey L.; Parisi, Joseph E; Boeve, Bradley F; Knopman, David S; Petersen, Ronald Carl; Jack, Clifford R Jr.; Dickson, Dennis W; Kantarci, Kejal M.

In: Journal of Neuroscience, Vol. 34, No. 49, 03.12.2014, p. 16247-16255.

Research output: Contribution to journalArticle

Murray ME, Przybelski SA, Lesnick TG, Liesinger AM, Spychalla A, Zhang B et al. Early Alzheimer’s disease neuropathology detected by proton MR spectroscopy. Journal of Neuroscience. 2014 Dec 3;34(49):16247-16255. https://doi.org/10.1523/JNEUROSCI.2027-14.2014
Murray, Melissa E ; Przybelski, Scott A. ; Lesnick, Timothy G. ; Liesinger, Amanda M. ; Spychalla, Anthony ; Zhang, Bing ; Gunter, Jeffrey L. ; Parisi, Joseph E ; Boeve, Bradley F ; Knopman, David S ; Petersen, Ronald Carl ; Jack, Clifford R Jr. ; Dickson, Dennis W ; Kantarci, Kejal M. / Early Alzheimer’s disease neuropathology detected by proton MR spectroscopy. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 49. pp. 16247-16255.
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