Amyotrophic lateral sclerosis of Guam: the nature of the neuropathological findings

Abstract

To elucidate the fundamental differences and similarities of the neuropathological features and etiopathogenesis of the amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) of Guam, we conducted a topographic, quantitative and histological investigation of tau-containing neurons, neurofibrillary tangles (NFTs), Bunina bodies and ubiquitinated inclusion bodies in 27 non-ALS non-PDC Guamanian subjects, as well as 10 Guam ALS patients, 28 PDC patients, and 5 patients with combined ALS and PDC (ALS-PDC). The topographic distribution of NFTs was basically the same in each disease and also in the non-ALS non-PDC group. There were relatively few, if any, NFTs in non-ALS non-PDC subjects and ALS patients, but there were many, especially in the frontal and temporal cortex, in Guam PDC and ALS-PDC patients. The histological and ultrastructural features of Bunina bodies in Guam ALS and ALS-PDC patients were similar to those reported in classic ALS. The ratio of occurrence of the inclusion in Guam ALS and ALS-PDC patients was similar to that reported so far in classic ALS. Ubiquitinated skein-like inclusion bodies were observed in the spinal anterior horn cells in Guam ALS and ALS-PDC patients. These findings indicate that classic ALS does exist on Guam, that NFTs in Guam ALS patients are merely a background feature widely dispersed in the population, that the mechanism of neuronal degeneration of Guam ALS is basically different from that of PDC, and that Guam ALS occurs initially are classic ALS.

Magnesium deficiency over generations in rats with special references to the pathogenesis of the parkinsonism–dementia complex and amyotrophic lateral sclerosis of Guam

“…In addition, declining trends in incidence rates are far less striking for patients with PDC than for ALS on Guam 25 . These findings altogether might indicate that the pathogenesis of ALS on Guam is different from that of PDC, as we have reported previously 35 …”

“…Motor neurons, such as anterior horn cells, were unremarkable in our study, although the substantia nigra exhibited a significant loss of dopaminergic neurons. Regarding the identification of PDC and ALS on Guam, the present authors advocate that ALS on Guam is basically different from PDC, based on the findings that the neurofibrillary tangles observed in ALS patients are merely a background feature that is widely distributed in the population 35 . In addition, declining trends in incidence rates are far less striking for patients with PDC than for ALS on Guam 25 .…”

Amyotrophic lateral sclerosis and parkinsonism‐dementia complex of the Hohara focus of the Kii Peninsula: A multiple proteinopathy?

“…Abundant NFTs were shown throughout the brains of Guamanian patients with PDC, whereas in the brains of Guamanian patients with ALS, the amount of NFTs was reported to be the same as that in the brains of healthy Chamorros. On the basis of these findings, Anderson et al and Oyanagi et al proposed a hypothesis that the appearance of a considerable number of NFTs was not a pathologically specific finding of Guamanian ALS but instead represented background changes of the brains of both healthy and diseased Chamorros . Oyanagi et al furthered this hypothesis and concluded that ALS in Guam is similar to the classical ALS‐associated NFT pathology that is common in Chamorros .…”

“…On the basis of these findings, Anderson et al and Oyanagi et al proposed a hypothesis that the appearance of a considerable number of NFTs was not a pathologically specific finding of Guamanian ALS but instead represented background changes of the brains of both healthy and diseased Chamorros. 6,7 Oyanagi et al furthered this hypothesis and concluded that ALS in Guam is similar to the classical ALS-associated NFT pathology that is common in Chamorros. 6,7 In our previous studies of the brains of Kii ALS/PDC cases from Hohara, 8,9 which is the eastern focus of Kii ALS, the number of NFTs in the brains varied from minimal to abundant, whereas, in the brains of non-ALS/PDC patients of this focus, the number and distribution of NFTs were almost the same as those of Japanese controls from other areas.…”

Neurofibrillary tangles in ALS and parkinsonism–dementia complex focus in Kii, Japan

“…NFTs appeared at earlier ages and higher frequencies in the Chamorro population than in the Japanese and English populations (see figure 2). In 1994, Oyanagi et al 8 examined NFTs of the brains of 36 Chamorro individuals in Guam, including 7 cases of ALS, 6 cases of PDC, 3 cases of ALS/PDC, and 20 cases without ALS/PDC. In 1994, Oyanagi et al 8 examined NFTs of the brains of 36 Chamorro individuals in Guam, including 7 cases of ALS, 6 cases of PDC, 3 cases of ALS/PDC, and 20 cases without ALS/PDC.…”