Related Brain Diseases

Since 1990, CurePSP has helped thousands of people with PSP, CBD and related brain diseases. While progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA) remain the prime focus of the Foundation, CurePSP has expanded its mission to include:

Argyrophilic Grain Disease (AGD)
Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC)
Guadelupean Tauopathy (GT)
Pallidal Degeneration (PaD)

Those living with AGD will primarily benefit through CurePSP's expanded education program, while ALS/PDC and GT have been added to the Foundation's research mission.

These mission expansions enable CurePSP to serve more patients and families with PSP, CBD and related diseases.

Argyrophilic Grain Disease (AGD)

Argyrophilic grain disease (aka Braaks Disease) is a neuro-degenerative brain disease which is not fully characterized. A sporadic late-onset form of dementia characterised by a neuro-degenerative process, which mainly affects limbic structures (amygdala, hippocampus and mediobasal temporal/entorhinal cortex).

It is named after silver-staining (argyrophilic) grains or coiled bodies within the cytoplasm of neurons that consist mainly of tau protein isoforms with four microtubule-binding repeates (4-R tau).

Reduction of short-term memory, disorders of word finding, disorders of reading and writing, disorientation, behavioral disturbances (personality changes, emotional disorders with aggression and ill-temper) may precede or follow memory failure. Clinically it is hard to distinguish from late-onset AD.

The age of onset is around 70 years old. The duration of the disease is between 4 and 8 years.

Causes and Risk Factors
The disease is caused by neuron degeneration which is likely associated with dysfunction of tau protein. Grains are composed of abnormally phosphorylated tau protein with 4 repeats. Recent studies indicate that tau protein dysfunction in AGD in contrast to other 4-R-tauopathies (progressive supranuclear palsy, corticobasal degeneration).

The disease arises irrespective of the genetic background regarding tau H1 or H2 haplotypes, at the opposite of PSP and CBD (Miserez A. R. et al, 2003). Lack of relationship with apolipoprotein E4.

1 to 5% of AD patients (Togo T. et al, 2002).

Diagnostic Procedures
It is almost impossible to distinguish from late-onset Alzheimer’s disease. The diagnosis is almost entirely made by post-mortem examination. AGD lesions are found in about 5% of Alzheimer’s disease (Togo T. et al, 2002).

(Source: European Commission-financed Project - "Rare Forms of Dementia", as well as Alzheimer Europe)

Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC)

The Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) is a rare disease of the brain and spinal cord which occurs in residents of the US Territory of Guam. ALS/PDC causes progressive and fatal neurological disease in Chamorros, Filipinos and Caucasians which may begin as early as age 15 or as late as 88 years of age. Young and middle aged patients develop progressive and fatal ALS that paralyzes their movement, speaking, and swallowing.

Older patients experience Parkinsonism resembling Parkinson's disease and atypical Parkinsonism. They are disabled by progressive and fatal immobility. The eldest patients have Alzheimer-type dementia with progressive and fatal memory impairment and personal deterioration. All forms of ALS/PDC are unrelenting and in late stages, all patients are bedbound and require total care by their families and community agencies. Despite all efforts, they die from inanition and intercurrent infections. The pathology of ALS/PDC is unique among neurodegenerative diseases. It is a single disease which accumulates all the diverse and abnormal proteins that occur separately in Alzheimer's disease, Parkinson's disease, atypical Parkinsonism, and ALS and include 3R and 4R tau, Abeta, alpha-synuclein, ubiquitin and TDP-43. During monitoring by the National Institutes of Health on Guam from 1957 to 2008, the prevalence of ALS/PDC has declined. But the NIH did not determine the cause of ALS/PDC which could provide understanding of related diseases, and ALS/PDC remains common in elderly subjects. The etiology and pathogenesis of ALS/PDC remain uncertain, but understanding of them will surely advance understanding and cure of other common and related diseases.

Alternative Names
Lytico-bodig is the Chamorro terms for ALS/PDC. Lytico derives from the Spanish word paralytico meaning paralysis and refers to ALS. Bodig, from the Spanish bodega identifies those with Parkinsonism and dementia.

Diagnostic Tests and Coding
On Guam where ALS/PDC is common, local physicians and neurologists accurately identify its clinical features, its steady progress, its familial occurrence and the presence of a distinctive linear retinopathy that is present in one half of cases of ALS/PDC. In other places, where physicians are not familiar with ALS/PDC, they are apt to misdiagnose it as a more common neurodegenerative disease, like Alzheimer's or Parkinson's disease, atypical Parkinsonism including PSP and CBD, or classical ALS. Such misdiagnosis is particularly a problem for 60,000 Chamorros who have moved to the US mainland since World War II, but whose neurological illness was acquired on Guam before departure. Because there is no category for ALS/PDC, it is coded by its different phenotypes including ALS 33529; Parkinsonism unspecified, with and without dementia 3320; and dementia-degenerative/idiopathic 2900.

No treatment halts the relentless and fatal progress of ALS/PDC and its management is symptomatic and emphasizes good general health, nutrition and physical activity. Education, guidance and counseling are provided to patients and families by physicians and at a Public Health Dementia center. In late stages, assisting devices, gastrostomy and airway assistance may be required. In the terminal phase, hospice care permits a comfortable and dignified death.

In 2010, Chamorros older that 50, living on Guam and in the mainland US are at greatest risk of ALS/PDC. Most suffer dementia and many also have Parkinsonism. Their disease can be fulminant and fatal within 6 months or prolonged with survival of more than 20 years. The usual duration of ALS/PDC is 5 years.

(Source: John C. Steele, MD, Honorary Chairman, CurePSP)

Video: ALS/PDC - The Illness and the Odyssey
More Information: Explaining Lytico-bodig and its Importance to the World

(CurePSP provides links to other websites for informational purposes but is not responsible for their content.)