Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
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Progressive increase of iron deposits in the brain is characteristic of normal aging. When compared with normal aged subjects, increased levels of ferritin are significantly higher in the caudate, putamen, and globus pallidus of Alzheimer's disease (AD) patients (Dedman et al., 1992; Good et al., 1992; Bartzokis et al., 1994). In vivo control of iron deposition is therefore of particular importance for therapeutic strategies. Because of iron's paramagnetic characteristic, magnetic resonance imaging (MRI) can detect in vivo the naturally occuring brain depositions. Brain regions with high iron content have short relaxation times yielding a hypointense (dark) signal in T2*-weighted images as compared to region with low iron content (Drayer, 1989).

This effect is more prominent at high magnetic field because susceptibility effects such as iron-related T2 relaxation time decrease are at least linearly dependent on magnetic field strength (Fisel et al., 1991; Lee, 1991; Bartzokis et al., 1993; Lee et al., 1995; Schenck, 1995; Vymazal et al, 1995; Gati et al., 1997).

Bartzokis et al. (1994, 1997) suggests that future directions of in vivo evaluation of tissue iron with MR should focus on structures that are highly relevant for AD, such as the basal forebrain.

In particular, the nucleus basalis of Meynert, the largest source of cholinergic fibers in the brain, is affected in AD. There is a highly significant linear relationship between cortical volume and nucleus basalis cell number in controls and Alzheimer's disease patients (Cullen et al., 1997). This nucleus is not distinctly enough demarcated to be visualized at the macroscopic level but it is structurally and functionally closely associated with the ventral extension of the globus pallidus (below and rostral to the anterior commissure). Iron levels in the ventral globus pallidus are among the highest in the brain and are well visualized in humans with standard clinical magnets (1.5 T). These increased levels may be a marker of increased iron in the basal forebrain (Bartzokis, 1997). Iron deposition in these regions is difficult to visualize in vivo because of their small size. In vivo MR detection of iron in the basal forebrain cholinergic structures should be possible at higher magnetic field strength.

This issue therefore can be best adressed in an animal model.

Laboratory animals which present spontaneously or experimentally the neuropathological hallmarks of Alzheimer's disease are available in non human primates. A strepsirhine primate, the mouse lemur (Microcebus murinus), appears to be the only animal model presenting both senile plaques and neurofibrillary degeneration (Bons et al., 1991, 1994, 1995; Mestre et al., 1996). Its life expectancy is about 4 years in the wild. In captivity however, it lives up to about 13 years. Because of its small size, rapid maturity, fecundity, and relatively short life expectancy, the mouse lemur constitutes a useful model system for the study of normal and pathological cerebral aging. Cholinergic neurons have been observed in the mouse lemur brain with cholineacetyltransferase (ChAT) immunocytochemistry in the septum, the diagonal band of Broca, the nucleus accumbens, the nucleus basalis of Meynert, the caudate, the putamen, the globus pallidus, and the olfactory tubercle. In the aged mouse lemur, cytological changes and neuronal loss have been observed in these structures (Mestre and Bons, 1993). In the present study, we assessed iron in the basal forebrain of aged mouse lemurs and a related species, the dwarf lemur (Cheirogaleus medius) with both magnetic resonance microscopy (11.7 T) and histochemistry (table 1).

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