Longitudinal PET-MRI Reveals β-amyloid Deposition and RCBF Dynamics and Connects Vascular Amyloidosis to Quantitative Loss of Perfusion

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2014 Nov 11

PMID 25384087

Citations 61

Authors

Florian C Maier

Hans F Wehrl

Andreas M Schmid

Julia G Mannheim

Stefan Wiehr

Chommanad Lerdkrai

Carsten Calaminus

Anke Stahlschmidt

Lan Ye

Michael Burnet

Detlef Stiller

Osama Sabri

Gerald Reischl

Mathias Staufenbiel

Olga Garaschuk

Mathias Jucker

Bernd J Pichler

Affiliations

Soon will be listed here.

Abstract

The dynamics of β-amyloid deposition and related second-order physiological effects, such as regional cerebral blood flow (rCBF), are key factors for a deeper understanding of Alzheimer's disease (AD). We present longitudinal in vivo data on the dynamics of β-amyloid deposition and the decline of rCBF in two different amyloid precursor protein (APP) transgenic mouse models of AD. Using a multiparametric positron emission tomography and magnetic resonance imaging approach, we demonstrate that in the presence of cerebral β-amyloid angiopathy (CAA), β-amyloid deposition is accompanied by a decline of rCBF. Loss of perfusion correlates with the growth of β-amyloid plaque burden but is not related to the number of CAA-induced microhemorrhages. However, in a mouse model of parenchymal β-amyloidosis and negligible CAA, rCBF is unchanged. Because synaptically driven spontaneous network activity is similar in both transgenic mouse strains, we conclude that the disease-related decline of rCBF is caused by CAA.

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References

Maeda J, Ji B, Irie T, Tomiyama T, Maruyama M, Okauchi T . Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer's disease enabled by positron emission tomography. J Neurosci. 2007; 27(41):10957-68. PMC: 6672864. DOI: 10.1523/JNEUROSCI.0673-07.2007. View

Meyer E . Simultaneous correction for tracer arrival delay and dispersion in CBF measurements by the H215O autoradiographic method and dynamic PET. J Nucl Med. 1989; 30(6):1069-78. View

Snellman A, Rokka J, Lopez-Picon F, Eskola O, Wilson I, Farrar G . Pharmacokinetics of [¹⁸F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2012; 39(11):1784-95. DOI: 10.1007/s00259-012-2178-9. View

Kwong K, Chesler D, Weisskoff R, Donahue K, Davis T, Ostergaard L . MR perfusion studies with T1-weighted echo planar imaging. Magn Reson Med. 1995; 34(6):878-87. DOI: 10.1002/mrm.1910340613. View

Villain N, Chetelat G, Grassiot B, Bourgeat P, Jones G, Ellis K . Regional dynamics of amyloid-β deposition in healthy elderly, mild cognitive impairment and Alzheimer's disease: a voxelwise PiB-PET longitudinal study. Brain. 2012; 135(Pt 7):2126-39. DOI: 10.1093/brain/aws125. View

Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S . Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996; 274(5284):99-102. DOI: 10.1126/science.274.5284.99. View

Zaim Wadghiri Y, Sigurdsson E, Sadowski M, Elliott J, Li Y, Scholtzova H . Detection of Alzheimer's amyloid in transgenic mice using magnetic resonance microimaging. Magn Reson Med. 2003; 50(2):293-302. DOI: 10.1002/mrm.10529. View

Iadecola C . Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci. 2004; 5(5):347-60. DOI: 10.1038/nrn1387. View

Toyama H, Ye D, Ichise M, Liow J, Cai L, Jacobowitz D . PET imaging of brain with the beta-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2005; 32(5):593-600. DOI: 10.1007/s00259-005-1780-5. View

10.

Kelly P, Bondolfi L, Hunziker D, Carver K, Maguire E, Abramowski D . Progressive age-related impairment of cognitive behavior in APP23 transgenic mice. Neurobiol Aging. 2002; 24(2):365-78. DOI: 10.1016/s0197-4580(02)00098-2. View

11.

Yan P, Bero A, Cirrito J, Xiao Q, Hu X, Wang Y . Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice. J Neurosci. 2009; 29(34):10706-14. PMC: 2756291. DOI: 10.1523/JNEUROSCI.2637-09.2009. View

12.

Yang J, Zaim Wadghiri Y, Hoang D, Tsui W, Sun Y, Chung E . Detection of amyloid plaques targeted by USPIO-Aβ1-42 in Alzheimer's disease transgenic mice using magnetic resonance microimaging. Neuroimage. 2011; 55(4):1600-9. PMC: 3085913. DOI: 10.1016/j.neuroimage.2011.01.023. View

13.

Jack Jr C, Knopman D, Jagust W, Shaw L, Aisen P, Weiner M . Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010; 9(1):119-28. PMC: 2819840. DOI: 10.1016/S1474-4422(09)70299-6. View

14.

Wegenast-Braun B, Fulgencio Maisch A, Eicke D, Radde R, Herzig M, Staufenbiel M . Independent effects of intra- and extracellular Abeta on learning-related gene expression. Am J Pathol. 2009; 175(1):271-82. PMC: 2708813. DOI: 10.2353/ajpath.2009.090044. View

15.

Winkler D, Bondolfi L, Herzig M, Jann L, Calhoun M, Wiederhold K . Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy. J Neurosci. 2001; 21(5):1619-27. PMC: 6762950. View

16.

Rosen R, Ciliax B, Wingo T, Gearing M, Dooyema J, Lah J . Deficient high-affinity binding of Pittsburgh compound B in a case of Alzheimer's disease. Acta Neuropathol. 2009; 119(2):221-33. PMC: 3045810. DOI: 10.1007/s00401-009-0583-3. View

17.

Garaschuk O, Milos R, Konnerth A . Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo. Nat Protoc. 2007; 1(1):380-6. DOI: 10.1038/nprot.2006.58. View

18.

Rojas S, Herance J, Gispert J, Abad S, Torrent E, Jimenez X . In vivo evaluation of amyloid deposition and brain glucose metabolism of 5XFAD mice using positron emission tomography. Neurobiol Aging. 2013; 34(7):1790-8. DOI: 10.1016/j.neurobiolaging.2012.12.027. View

19.

Lilja A, Rojdner J, Mustafiz T, Thome C, Storelli E, Gonzalez D . Age-dependent neuroplasticity mechanisms in Alzheimer Tg2576 mice following modulation of brain amyloid-β levels. PLoS One. 2013; 8(3):e58752. PMC: 3598857. DOI: 10.1371/journal.pone.0058752. View

20.

Ikonomovic M, Klunk W, Abrahamson E, Mathis C, Price J, Tsopelas N . Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008; 131(Pt 6):1630-45. PMC: 2408940. DOI: 10.1093/brain/awn016. View