Argyrophilic Grain Disease (AGD)
by André Delacourte & Kurt Jellinger
New disease, which is not fully characterised. 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).
Symptoms and course
Reduction of short-term memory, disorders of word finding, disorders of reading and writing, disorientation, behavioural 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
Neuron degeneration 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).
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).
Care and treatment
Those related to patients affected by Alzheimer’s disease.
Ongoing research / clinical trials
Continued research on tau protein. Subclasses of AGD may exist, with a more diffuse forms of grain pathology (Maurage C. A. et al, 2003).
Due to the recent characterisation of this disease, there are no specific available services.
- Botez G et al. Clinical aspects of argyrophilic grain disease (German). Nervenarzt 2000; 71:38-43.
- Maurage C. A., Sergeant N., Schraen-Maschke S., Lebert F., Ruchoux M. M., Sablonniere B., Pasquier F. and Delacourte A. (2003) Diffuse form of argyrophilic grain disease: a new variant of four-repeat tauopathy different from limbic argyrophilic grain disease. Acta Neuropathol (Berl)
- Miserez A. R., Clavaguera F., Monsch A. U., Probst A. and Tolnay M. (2003) Argyrophilic grain disease: molecular genetic difference to other four-repeat tauopathies. Acta Neuropathol (Berl) 106, 363-366.
- Togo T et al. Argyrophilic grain disease is a sporadic 4-repeat tauopathy. J Neuropathol Exp Neurol. 2002; 61:547-56.
- Togo T et al. Argyrophilic grain disease: neuropathology, frequency in a dementia brain bank and lack of relationship with apolipoprotein E. Brain Pathol. 2002; 12:45-52.
- Tolnay M et al. Argyrophilic grain disease: widespread hyperphosphorylation of tau protein in limbic neurons. Acta Neuropathol 1997; 93:477-84.
- Tolnay M et al. Argyrophilic grain disease and Alzheimer's disease are distinguished by their different distribution of tau protein isoforms. Acta Neuropathol 2002; 104:425-34.
Last Updated: vendredi 09 octobre 2009