Abstract
The development of a noninvasive method to detect early, subtle changes in the brains of patients with Alzheimer’s disease (AD) would have considerable clinical value as therapy. This therapy is most likely to be successful if intervention could occur before neurons were irreversibly damaged or lost. An ideal biological neuroimaging marker would be an early, sensitive, and valid indicator of brain changes, capable of discriminating the effects of normal aging. The introduction of high field-strength clinical magnetic resonance imaging (MRI) systems now offer a powerful new noninvasive tool that may be capable of detecting brain pathology resulting from AD. Here we present results from high field-strength MRI in transgenic mice along with a new MRI technique for imaging brain iron. The successful translation of this research to the clinic could prove important to both the early diagnosis and monitoring of the efficacy of potential therapies in humans.
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Bartzokis G., Sultzer D., Cummings J., Holt L. E., Hance D. B., Henderson V. W., and Mintz J. (2000) In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging. Arch. Gen. Psychiatry 57, 47–53.
Cataldo A., Peterhoff C., Troncoso J., T G-I., Hyman B., and Nixon R. (2000) Endocytic pathway abnormalities precede beta-amyloid deposition in sporadic Alzheimer’s disease: differential effects of APOE genotype and presenilin mutations. Am. J. Pathol. 157, 277–286.
Connor J. R., Menzies S. L., St Martin S. M., and Mufson E. J. (1990) Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains. J. Neurosci. Res. 27, 595–611.
Connor J. R., Menzies, S. L., St Martin S. M., and Mufson E. J. (1992). A histochemical study of iron, transferrin, and ferritin in Alzheimer’s diseased brains. J. Neurosci. Res. 31, 75–83.
Falangola M., Dyakin V., Lee S. P., Bogart A., Estok K., Duff K., et al. (2003) Quantitative T2 evidence for selective hippocampal involvement in a transgenic mouse model of AD. International Society for Magnetic Resonance in Medicine 11th Scientific Meeting, Toronto, Canada, p. 2037.
Grohn O. H., Kettunen M. I., Penttonen M., Oja J. M., van Zijl P. C., and Kauppinen R. A. (2000) Graded reduction of cerebral blood flow in rat as detected by the nuclear magnetic resonance relaxation time T2: a theoretical and experimental approach. J. Cereb. Blood Flow Metab. 20, 316–326.
Haroutunian V., Perl D. P., Purohit D. P., et al. (1998) Regional distribution of neuritic plaques in the non-demented elderly and subjects with very mild Alzheimer disease [see Comments]. Arch. Neurol. 55, 1185–1191.
Helpern J. A., Dereski M. O., Knight R. A., Ordidge R. J., Chopp M., and Qing Z. X. (1993) Histopathological correlations of nuclear magnetic resonance imaging parameters in experimental cerebral ischemia. Mag. Reson. Imaging 11, 241–246.
Holcomb L., Gordon M. N., McGowan E., et al. (1998) Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat. Med. 4, 97–100.
Jensen J. H. and Chandra R. (2000) NMR relaxation in tissues with weak magnetic inhomogeneities. Magn. Reson. Med. 44, 144–156.
Knight R. A., Dereski M. O., Helpern J. A., Ordidge R. J. and Chopp M. (1994) Magnetic resonance imaging assessment of evolving focal cerebral ischemia: Comparson with histopathology in rats. Stroke 25(6), 1252–1262.
Knight R. A., Ordidge R. J., Helpern J. A., Chopp M., Rodolosi L. C., and Peck D. (1991) Temporal evolution of ischemic damage in rat brain measured by proton nuclear magnetic resonance imaging. Stroke 22, 802–808.
Kurt M. A., Davies D. C., Kidd M., Duff K., Rolph S. C., Jennings K. H., and Howlett D. R. (2001) Neurodegenerative changes associated with beta-amyloid deposition in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgene. Exp. Neurol. 171, 59–71.
McGowan E., Sanders S., Iwatsubo T., et al. (1999) Amyloid phenotype characterization of transgenic mice overexpressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes. Neurobiol. Dis. 6, 231–244.
Morris, J. C., Storandt M., McKeel D. W., et al. (1996) Cerebral amyloid deposition and diffuse plaques in “normal” aging: evidence for presymptomatic and very mild Alzheimer’s disease. Neurology 46, 707–719.
Ordidge R. J., Helpern J. A., Knight R. A., Qing Z., and Welch K.M.A. (1991) Investigation of cerebral ischemia using magnetization transfer contrast (MTC) MR imaging. Magn. Reson. Imaging 9, 895–902.
Takeuchi A., Irizarry M. C., Duff K., et al. (2000) Age-related amyloid beta deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid beta precursor protein Swedish mutant is not associated with global neuronal loss. Am. J. Pathol. 157, 331–339.
Wengenack T. M., Whelan S., Curran G. L., Duff K. E., and Poduslo J. F. (2000) Quantitative histological analysis of amyloid deposition in Alzheimer’s double transgenic mouse brain. Neuroscience 101, 939–944.
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Helpern, J.A., Jensen, J., Lee, SP. et al. Quantitative MRI assessment of Alzheimer’s disease. J Mol Neurosci 24, 45–48 (2004). https://doi.org/10.1385/JMN:24:1:045
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DOI: https://doi.org/10.1385/JMN:24:1:045