MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer's and Huntingon's disease

Citation
G. Bartzokis et Ta. Tishler, MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer's and Huntingon's disease, CELL MOL B, 46(4), 2000, pp. 821-833
Citations number
102
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELLULAR AND MOLECULAR BIOLOGY
ISSN journal
01455680 → ACNP
Volume
46
Issue
4
Year of publication
2000
Pages
821 - 833
Database
ISI
SICI code
0145-5680(200006)46:4<821:MEOBGF>2.0.ZU;2-I
Abstract
Background: The basal ganglia contain the highest levels of iron in the bra in and post-mortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with neurodegenerative disorders such as Alzheime r's disease (AD) and Huntington's disease (HD). Iron can catalyze free radi cal reactions and may contribute to oxidative damage observed in ND and HD brain. Magnetic resonance imaging (MRI) can quantify transverse relaxation rates, which can be used to quantify tissue iron stores as well as evaluate increases in MR-visible water tan indicator of tissue damage). Methods: A magnetic resonance imaging (MRI) method termed the field dependent relaxati on rate increase (FDRI) was employed which quantifies the iron content of f erritin molecules (ferritin iron) with specificity through the combined use of high and low field-strength MRI instruments. Three basal ganglia struct ures (caudate, putamen and globus pallidus) and one comparison region (fron tal lobe white matter) were evaluated. Thirty-one patients with AD and a gr oup of 68 older control subjects, and 11 patients with HD and a group of 27 adult controls participated (4 subjects overlap between AD and HD controls ). Results: Compared to their respective normal control groups, increases i n basal ganglia FDRI levels were seen in both AD and HD. FDRI levels were s ignificantly increased in the caudate (p = 0.007) and putamen (p = 0.008) o f patients with AD with a trend toward an increase in the globus pallidus ( p = 0.13). In the patients with HD, all three basal ganglia regions showed highly significant FDRI increases (p<0.001) and the magnitude of the increa ses were 2 to 3 times larger than those observed in AD versus control group comparison. For both HD and AD subjects, the basal ganglia FDRI increase w as not a generalized phenomenon, as frontal lobe white matter FDRI levels w ere decreased in HD (p = 0.015) and remained unchanged in AD. Significant l ow field relaxation rate decreases (suggestive of increased MR-visible wate r and indicative of tissue damage) were seen in the frontal lobe white matt er of both HD and AD but only the HD basal ganglia showed such decreases. C onclusions: The data suggest that basal ganglia ferritin iron is increased in HD and PLD. Furthermore, the increased iron levels do not appear to be a byproduct of the illness itself since they seem to be present at the onset of the diseases, and thus may be considered a putative risk factor. Publis hed post-mortem studies suggest that the increase in basal ganglia ferritin iron may occur through different mechanisms in HD and AD. Consistent with the known severe basal ganglia damage, only HD basal ganglia demonstrated s ignificant decreases in low field relaxation rates. MRI can be used to diss ect differences in tissue characteristics, such as ferritin iron and MR-vis ible water, and thus could help clarify neuropathologic processes in vivo. Interventions aimed at decreasing brain iron levels, as well as reducing th e oxidative stress associated with increased iron levels, may offer novel w ays to delay the rate of progression and possibly defer the onset of AD and HD.