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Alzheimer-type pathology in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
1Department of Neurology, Osaka University Medical School, Japan.
Abstract:
A 53-year-old Japanese woman with a point mutation in mitochondrial DNA (tRNALeu(UUR), nt3243) consistent with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and Alzheimer-type brain pathology is reported. This woman had suffered myopathy and psychosis without any clinical evidence of, stroke-like episodes during the last 10 years of her life, and had died after an accident. At autopsy 30 h post mortem, a part of the brain was snap frozen for biochemical and histochemical studies, and the remaining part was processed for a routine examination and electron microscopy. In the brain there were no ischemic lesions. Instead, primitive/diffuse senile plaques were found throughout the brain, predominantly in the frontal and temporal lobes, while Alzheimer neurofibrillary tangles were found only in the parahippocampal gyrus. These plaques were positive for beta-protein and mostly negative for tau protein, ubiquitin, neurofilaments, alpha-choline acetyltransferase, and acetylcholinesterase. Mutations in codon 331 of the ND2 gene as well as codons 693, 713 and 717 of the beta-amyloid precursor protein gene, known to be responsible for some cases of familial Alzheimer disease, were not found. Furthermore, coincidental Down syndrome was ruled out by chromosome analysis. The results suggest a possible correlation between this mitochondrial DNA abnormality and Alzheimer-type pathology.
Insights
Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) with a mitochondrial DNA mutation showed Alzheimer-type brain pathology. This suggests a potential link between mitochondrial DNA abnormalities and Alzheimer disease.
Area of Science:
- Neurology
- Mitochondrial Biology
- Neurodegenerative Diseases
Background:
- Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disorder.
- Alzheimer-type pathology is characterized by amyloid plaques and neurofibrillary tangles.
- The co-occurrence of MELAS and Alzheimer pathology is rare and not well understood.
Observation:
- A 53-year-old woman with a known mitochondrial DNA mutation (nt3243) consistent with MELAS presented with myopathy and psychosis, but no stroke-like episodes.
- Autopsy revealed primitive/diffuse senile plaques positive for beta-protein, predominantly in the frontal and temporal lobes.
- Alzheimer neurofibrillary tangles were localized to the parahippocampal gyrus; no ischemic lesions were observed.
Findings:
- The patient's brain exhibited Alzheimer-type pathology, specifically beta-protein-positive senile plaques, without typical ischemic lesions.
- Genetic analysis ruled out common familial Alzheimer disease mutations and Down syndrome.
- Mitochondrial DNA abnormality was identified as the primary genetic factor.
Implications:
- This case suggests a potential correlation between mitochondrial DNA abnormalities, such as those found in MELAS, and the development of Alzheimer-type brain pathology.
- Further research is warranted to explore the mechanisms linking mitochondrial dysfunction to amyloid deposition and neurodegeneration.
- Understanding this connection could offer new insights into the pathogenesis of both mitochondrial diseases and Alzheimer disease.