Amyotrophic lateral sclerosis / Parkinsonism dementia complex of Guam

Guamanian ALS/PDC Amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam (ALS/PDC) is a chronic neurodegenerative disorder highly prevalent in the native Chamorro population of Guam island in the Western Pacific (Hirano et al., 1961).

The etiopathogenesis of this disorder is not yet elucidated, although it has been hypothesized that environmental factors such as aluminium or neurotoxins might be involved (Garruto et al., 1991).

Clinically, Guamanian amyotrophic lateral sclerosis (ALS) is indistinguishable from sporadic ALS and presents with fasciculations and lower and upper motor neuron signs. Parkinsonism-dementia is characterized by an insidious progressive mental decline and extrapyramidal signs (Hirano et al., 1961; Chen and Chase, 1986). Both aspects of the disease are frequently associated, but they are known to occur separately.

Neuropathologically, Guamanian ALS/PDC shows a severe cortical atrophy and neuronal loss. The neuropathological hallmark of ALS/PDC is the widespread NFT formation, especially in the isocortex and hippocampal formation (Hirano et al., 1961; 1968). Although NFT are present in large numbers in both AD and ALS/PDC, these two conditions are distinguished by differential NFT laminar distribution patterns and densities in neocortex. NFT are preferentially distributed within layers II-III in the isocortical areas of Guamanian ALS/PDC cases and are relatively sparser in layers V-VI, whereas NFT are denser in layers V-VI than layers II-III in AD cases (Hof et al., 1991; 1994b; Oyanagi et al., 1994).

The ultrastructure of NFT in Guamanian ALS/PDC consists of straight filaments and PHF (Rewcastle, 1991), and PHF have been shown to be essentially similar to those observed in AD (Hirano et al., 1968).

Immunohistochemical studies have also revealed that pathological tau proteins are present in NFT of ALS/PDC patients (Hof et al., 1994; Buée-Scherrer et al., 1995).

Biochemical studies demonstrate that a tau triplet is also found in ALS/PDC (Buée-Scherrer et al., 1995) (Type I signature). It is highly related immunologically to the AD triplet as demonstrated by using numerous phosphorylation-dependent antibodies (Buée-Scherrer et al., 1995; Mawal-Dewan et al., 1996). In contrast to AD patients where the tau triplet is found mostly in cortical regions, a similar triplet is strongly detected in both cortical and subcortical areas in Guamanian patients. The tau profile differs quantitatively from case to case, demonstrating that the AD-related tau triplet has a heterogeneous regional distribution. Thus, the tau triplet found in Guam ALS/PDC is similar to that observed in AD, although the regional distribution of tau proteins differs in these disorders (Buée-Scherrer et al., 1995; Mawal-Dewan et al., 1996). Since the etiology of Guamanian ALS/PDC is different from AD, with no amyloid, this also demonstrates that neurofibrillary degeneration with a Tau triplet 60, 64, 69 is very likely a similar response to different types of neuronal insults.

See Tauopathies