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Assay Development for High Content Quantification of Sod1 Mutant Protein Aggregate Formation in Living Cells
Published on: October 4, 2017
SOD1 and cognitive dysfunction in familial amyotrophic lateral sclerosis
1MRC Centre for Neurodegeneration, Research, PO 77, Dept. of Psychology, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK.
Journal of Neurology
|March 3, 2009
Summary
Cognitive impairment in familial ALS (FALS) varies by genetic mutation. Patients with SOD1 gene mutations show fewer cognitive changes than those without, indicating genetic factors influence ALS cognitive profiles.
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- Amyotrophic Lateral Sclerosis (ALS) can present with cognitive dysfunction, ranging from frontotemporal dementia (ALS-FTD) to milder executive deficits (ALSCi).
- While familial ALS (FALS) can have a history of FTD, ALS-FTD, or both, ALS-FTD in superoxide dismutase-1 (SOD1) mutation carriers (SOD1 FALS) is rarely reported.
- This study investigates cognitive changes in different FALS genetic subtypes.
Purpose of the Study:
- To test the hypothesis that non-SOD1 FALS patients exhibit cognitive deficits (ALSCi).
- To determine if SOD1 FALS patients show minimal or no cognitive changes.
- To compare cognitive profiles across sporadic ALS (SALS), SOD1 FALS, non-SOD1 FALS, and controls.
Main Methods:
- Administered a comprehensive neuropsychological test battery.
- Included 41 SALS patients, 35 controls, 7 SOD1 FALS patients, and 10 non-SOD1 FALS patients.
- Groups were matched for age, gender, premorbid IQ, anxiety, and depression.
Main Results:
- Non-SOD1 FALS patients demonstrated impaired verbal fluency and naming, with increased executive behavioral problems compared to controls.
- SOD1 FALS patients showed no significant cognitive deficits.
- All ALS groups exhibited higher apathy and emotional lability than controls, while memory, language comprehension, and visuospatial skills remained intact.
Conclusions:
- Individuals with SOD1 mutations are less prone to significant cognitive alterations in ALS.
- Cognitive abnormalities in ALS are heterogeneous and influenced by underlying genetic variations.
- Findings suggest genetic background plays a crucial role in the manifestation of extra-motor symptoms in ALS.
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