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Neurofibrillary tangles in Niemann-Pick disease type C
K Suzuki1, C C Parker, P G Pentchev
1Department of Pathology, School of Medicine, University of North Carolina at Chapel Hill 27599-7525, USA.
Acta Neuropathologica
|January 1, 1995
Summary
Niemann-Pick disease type C (NPC) involves cholesterol transport errors, leading to lysosomal accumulation. Researchers discovered neurofibrillary tangles (NFTs) in NPC brains, suggesting metabolic issues, not just amyloid, can cause NFTs.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Niemann-Pick disease type C (NPC) is a rare, autosomal recessive lipid storage disorder.
- NPC is characterized by defective cellular cholesterol trafficking and lysosomal accumulation of unesterified cholesterol.
- Unlike NPC types A and B, NPC does not stem from a sphingomyelinase genetic defect.
Observation:
- Neurofibrillary tangles (NFTs) were identified in neuropathological studies of NPC patients.
- These NFTs were not associated with beta-amyloid deposits.
- NFTs were prevalent in specific brain regions including the cerebral cortex, basal ganglia, thalamus, and hypothalamus, and even in the spinal cord in severe cases.
Findings:
- NFTs in NPC patients immunostained with Alz 50 and comprised paired helical filaments.
- The distribution of NFTs often overlapped with swollen storage neurons, with NFTs found within these cells.
- Neurons containing NFTs were observed even without apparent cellular swelling, indicating NFTs can occur independently of gross storage morphology.
Implications:
- The presence of NFTs alongside neuronal storage in NPC suggests that disrupted cholesterol metabolism and lysosomal trafficking may contribute to NFT formation.
- This finding challenges the necessity of beta-amyloid deposits for NFT development.
- NFT formation might represent a general neuronal response to chronic, slow-progressing metabolic disturbances, irrespective of the specific underlying cause.