Brain, Vol. 122, No. 8, 1519-1531,
August 1999
© 1999 Oxford University Press
Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET
Implications for Alzheimer's disease
.
1 INSERM U320 and 2 CEA LRA 10V, Centre Cyceron, University of Caen, France and 3 Department of Neurology, Research Institute of Brain and Blood Vessels, Akita, Japan
Correspondence to:
Dr J. C. Baron, INSERM U320, Centre Cyceron, BP 5229, 14074 Caen cedex, France. E-mail: baron{at}cyceron.fr
Temporoparietal glucose hypometabolism, neuronal loss in the basal forebrain cholinergic structures and preferential accumulation of neurofibrillary tangles in the rhinal cortex (i.e. in the entorhinal and perirhinal cortices) are three early characteristics of Alzheimer's disease. Based on studies of the effects of neurotoxic lesions in baboons, we previously concluded that damage to the cholinergic structures plays, at best, a marginal role in the association neocortex hypometabolism of Alzheimer's disease. In the present study, we have assessed the remote metabolic effects of bilateral neurotoxic lesions of both entorhinal and perirhinal cortices. Using coronal PET coregistered with MRI, the cerebral metabolic rate for glucose (CMRglc) was measured before surgery and sequentially for 2–3 months afterward (around days 30, 45 and 80). Compared with sham-operated baboons, the lesioned animals showed a significant and long-lasting CMRglc decline in a small set of brain regions, especially in the inferior parietal, posterior temporal, posterior cingulate and associative occipital cortices, as well as in the posterior hippocampal region, all of which also exhibit glucose hypometabolism in Alzheimer's disease. Remarkably, the degree of CMRglc decline in four of these regions significantly correlated with the severity of histologically determined damage in the rhinal cortex, strongly supporting the specificity of the observed metabolic effects. There were also differences between the metabolic pattern observed in the lesioned animals and that classically reported in Alzheimer's disease; for instance, the hypometabolism we found in the stratum has not been reported in early Alzheimer's disease, although this structure can be affected in late stages of the disease and has direct anatomical connections with the rhinal cortex. Nevertheless, this study shows for the first time that the temporoparietal and hippocampal hypometabolism found in Alzheimer's disease may partly result from neuroanatomical disconnection with the rhinal cortex. This, in turn, further strengthens the hypothesis that neuronal damage and dysfunction in the rhinal cortices play a major role in the expression of Alzheimer's disease.
rhinal cortex; baboon; CMRglc; [18F]fluoro-2-deoxy-D-glucose
ANOVA = analysis of variance; CMRglc = cerebral metabolic rate for glucose; FDG = [18F]fluoro-2-deoxy-D-deoxyglucose; MRA = magnetic resonance angiography; pAC = posterior edge of the anterior commissure; RH = animal which reveived a lesion in the rhinal cortex; SH = sham-operated animal
* Present address: Section of Neuropsychology, Tohoku University School of Medicine, Sendai, Japan
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Villain, B. Desgranges, F. Viader, V. de la Sayette, F. Mezenge, B. Landeau, J.-C. Baron, F. Eustache, and G. Chetelat Relationships between Hippocampal Atrophy, White Matter Disruption, and Gray Matter Hypometabolism in Alzheimer's Disease J. Neurosci., June 11, 2008; 28(24): 6174 - 6181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Le Ber, A. Camuzat, D. Hannequin, F. Pasquier, E. Guedj, A. Rovelet-Lecrux, V. Hahn-Barma, J. van der Zee, F. Clot, S. Bakchine, et al. Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study Brain, March 1, 2008; 131(3): 732 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chetelat, B. Desgranges, B. Landeau, F. Mezenge, J. B. Poline, V. de la Sayette, F. Viader, F. Eustache, and J.-C. Baron Direct voxel-based comparison between grey matter hypometabolism and atrophy in Alzheimer's disease Brain, January 1, 2008; 131(1): 60 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsuda Role of Neuroimaging in Alzheimer's Disease, with Emphasis on Brain Perfusion SPECT J. Nucl. Med., August 1, 2007; 48(8): 1289 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Kepe, J. R. Barrio, S.-C. Huang, L. Ercoli, P. Siddarth, K. Shoghi-Jadid, G. M. Cole, N. Satyamurthy, J. L. Cummings, G. W. Small, et al. Serotonin 1A receptors in the living brain of Alzheimer's disease patients PNAS, January 17, 2006; 103(3): 702 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bartzokis, P. H. Lu, D. H. Geschwind, N. Edwards, J. Mintz, and J. L. Cummings Apolipoprotein E Genotype and Age-Related Myelin Breakdown in Healthy Individuals: Implications for Cognitive Decline and Dementia Arch Gen Psychiatry, January 1, 2006; 63(1): 63 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Buckner, A. Z. Snyder, B. J. Shannon, G. LaRossa, R. Sachs, A. F. Fotenos, Y. I. Sheline, W. E. Klunk, C. A. Mathis, J. C. Morris, et al. Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory J. Neurosci., August 24, 2005; 25(34): 7709 - 7717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Guedj, D. Taieb, C. De Laforte, M. Ceccaldi, O. Mundler, Y. Krausz, N. Freedman, and O. Bonne Similitude of Brain Perfusion Pattern in Hypothyroidism and Early Alzheimer's Disease: Physiopathologic Considerations J. Nucl. Med., July 1, 2005; 46(7): 1247 - 1248. [Full Text] [PDF]
|
|
|
|
 |
|
 C Pennanen, C Testa, M P Laakso, M Hallikainen, E-L Helkala, T Hanninen, M Kivipelto, M Kononen, A Nissinen, S Tervo, et al. A voxel based morphometry study on mild cognitive impairment J. Neurol. Neurosurg. Psychiatry, January 1, 2005; 76(1): 11 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Liu, K. Iqbal, I. Grundke-Iqbal, G. W. Hart, and C.-X. Gong O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease PNAS, July 20, 2004; 101(29): 10804 - 10809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Meguro, M. Meguro, Y. Tanaka, K. Akanuma, K. Yamaguchi, and M. Itoh Risperidone is Effective for Wandering and Disturbed Sleep/Wake Patterns in Alzheimer's Disease J Geriatr Psychiatry Neurol, June 1, 2004; 17(2): 61 - 67. [Abstract] [PDF]
|
|
|
|
|
|
M. D. Greicius, G. Srivastava, A. L. Reiss, and V. Menon Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI PNAS, March 30, 2004; 101(13): 4637 - 4642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mosconi, A. Pupi, M. T. R. De Cristofaro, M. Fayyaz, S. Sorbi, and K. Herholz Functional Interactions of the Entorhinal Cortex: An 18F-FDG PET Study on Normal Aging and Alzheimer's Disease J. Nucl. Med., March 1, 2004; 45(3): 382 - 392. [Abstract] [Full Text]
|
|
|
|
|
|
E. M. Reiman, K. Chen, G. E. Alexander, R. J. Caselli, D. Bandy, D. Osborne, A. M. Saunders, and J. Hardy Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia PNAS, January 6, 2004; 101(1): 284 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lustig, A. Z. Snyder, M. Bhakta, K. C. O'Brien, M. McAvoy, M. E. Raichle, J. C. Morris, and R. L. Buckner Functional deactivations: Change with age and dementia of the Alzheimer type PNAS, November 25, 2003; 100(24): 14504 - 14509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chetelat, B. Desgranges, V. de la Sayette, F. Viader, K. Berkouk, B. Landeau, C. Lalevee, F. Le Doze, B. Dupuy, D. Hannequin, et al. Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment Brain, September 1, 2003; 126(9): 1955 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Matthews, E. R. Siemers, and P. D. Mozley Imaging-Based Measures of Disease Progression in Clinical Trials of Disease-Modifying Drugs for Alzheimer Disease Am J Geriatr Psychiatry, April 1, 2003; 11(2): 146 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. ALIEV, D. SEYIDOVA, M. L. NEAL, J. SHI, B. T. LAMB, S. L. SIEDLAK, H. V. VINTERS, E. HEAD, G. PERRY, J. C. LAMANNA, et al. Atherosclerotic Lesions and Mitochondria DNA Deletions in Brain Microvessels as a Central Target for the Development of Human AD and AD-Like Pathology in Aged Transgenic Mice Ann. N.Y. Acad. Sci., November 1, 2002; 977(1): 45 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J-C Baron Hippocampal atrophy and neocortical dysfunction in early Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, November 1, 2002; 73(5): 470 - 471. [Full Text]
|
|
|
|
|
|
X. Blaizot, K. Meguro, I. Millien, J. C. Baron, and C. Chavoix Correlations between Visual Recognition Memory and Neocortical and Hippocampal Glucose Metabolism after Bilateral Rhinal Cortex Lesions in the Baboon: Implications for Alzheimer's Disease J. Neurosci., November 1, 2002; 22(21): 9166 - 9170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Okamura, H. Arai, M. Maruyama, M. Higuchi, T. Matsui, H. Tanji, T. Seki, H. Hirai, H. Chiba, M. Itoh, et al. Combined Analysis of CSF Tau Levels and [123I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer's Disease Am J Psychiatry, March 1, 2002; 159(3): 474 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsuda, N. Kitayama, T. Ohnishi, T. Asada, S. Nakano, S. Sakamoto, E. Imabayashi, and A. Katoh Longitudinal Evaluation of Both Morphologic and Functional Changes in the Same Individuals with Alzheimer's Disease J. Nucl. Med., March 1, 2002; 43(3): 304 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Meguro, C LeMestric, B Landeau, B Desgranges, F Eustache, and J-C Baron Relations between hypometabolism in the posterior association neocortex and hippocampal atrophy in Alzheimer's disease: a PET/MRI correlative study J. Neurol. Neurosurg. Psychiatry, September 1, 2001; 71(3): 315 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. de Leon, A. Convit, O. T. Wolf, C. Y. Tarshish, S. DeSanti, H. Rusinek, W. Tsui, E. Kandil, A. J. Scherer, A. Roche, et al. Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-D-glucose/positron-emission tomography (FDG/PET) PNAS, August 23, 2001; (2001) 191044198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Small, L. M. Ercoli, D. H. S. Silverman, S.-C. Huang, S. Komo, S. Y. Bookheimer, H. Lavretsky, K. Miller, P. Siddarth, N. L. Rasgon, et al. From the Cover: Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease PNAS, May 23, 2000; 97(11): 6037 - 6042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. de Leon, A. Convit, O. T. Wolf, C. Y. Tarshish, S. DeSanti, H. Rusinek, W. Tsui, E. Kandil, A. J. Scherer, A. Roche, et al. Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-D-glucose/positron-emission tomography (FDG/PET) PNAS, September 11, 2001; 98(19): 10966 - 10971. [Abstract] [Full Text] [PDF]
|
|