Enduring involvement of tau, β-amyloid, α-synuclein, ubiquitin and TDP-43 pathology in the amyotrophic lateral sclerosis/parkinsonism–dementia complex of Guam (ALS/PDC)

• Published in: Acta neuropathologica Vol. 116; no. 6; pp. 625 - 637
• Main Authors: Miklossy, Judith, Steele, John C., Yu, Sheng, McCall, Sherman, Sandberg, Glenn, McGeer, Edith G., McGeer, Patrick L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.12.2008
• Subjects: Adult; Aged; Aged, 80 and over; alpha-Synuclein - metabolism; Amyloid beta-Peptides - metabolism; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Autopsy; Brain - metabolism; Brain - pathology; Brain Chemistry; Dementia - metabolism; Dementia - pathology; DNA-Binding Proteins - metabolism; Female; Guam; Humans; Immunohistochemistry; Inclusion Bodies - metabolism; Inclusion Bodies - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neurofibrillary Tangles - metabolism; Neuroglia - metabolism; Neuroglia - pathology; Neurons - metabolism; Neurons - pathology; Neurosciences; Original Paper; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - pathology; Pathology; tau Proteins - metabolism; Ubiquitin - metabolism; Guam; Parkinsonism; α-Synuclein; Neurofibrillary tangles; Alzheimer’s disease; TDP-43; Tau; Coiled body; β-Amyloid protein
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-008-0439-2

Guam ALS/PDC is a severe tangle forming disorder endemic to Guam with features overlapping such neurodegenerative disorders as Alzheimer disease (AD), Parkinson disease (PD), progressive supranuclear palsy (PSP), ALS, corticobasal degeneration (CBD) and pallido-ponto-nigral degeneration (PPND). Since the prevalence is declining, we examined brain tissue from 35 clinically diagnosed Chamorro patients with ALS/PDC and two Chamorro controls autopsied between 1946 and 2006, to determine if distinct variations in the pathology could be identified up to this time. Although the age at autopsy increased by 4.5–5 years per decade, we identified no qualitative differences in pathological deposits with antibodies against tau, ubiquitin, Aβ, α-synuclein and TDP-43, indicating that these more recently identified proteins have been involved in the neuropathogenesis over the past 6 decades. Tau and TDP-43 positive neuronal, oligodendroglial and astrocytic inclusions involving multiple nerve fiber tracts occurred in both the ALS and PDC types, reinforcing the concept that these forms are part of the same disorder. The results obtained may help to define the commonality of the Guam disease with other tangle forming disorders and may help in monitoring the epidemiological changes that are taking place.