title: Mutations in Niemann Pick type C gene are risk factor for Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common form of dementia characterized by deterioration of memory and other cognitive domains which leads to death in 3-9years after diagnosis. In addition to mutations in APP, PSEN1 and PSEN2 genes, that cause early onset autosomal dominant AD, several genetic risk factors for late onset AD are now known. There is another distinctive neurodegenerative lysosomal storage disorder - Niemann-Pick type C (NPC) that is sometimes referred to as "Childhood Alzheimer's". NPC is autosomal recessive disease caused by mutations in the NPC1 or NPC2 genes. NPC and AD share some biochemical and pathological similarities which are discussed in this paper. On the other hand, there is a well documented connection between other autosomal recessive lysosomal storage disorder - Gaucher's disease (GD) and neurodegenerative disorder - Parkinson's disease (PD). It has been shown that GD patients have 20-fold increased life-time risk of developing PD. Surprisingly, even heterozygous carriers of mutations in glucocerebrosidase gene (GBA) have increased risk for developing PD. Having in mind above mentioned correlations, we hypothesized that heterozygous mutations in the NPC gene may act as an independent risk factor for Alzheimer's disease. If true, this would expand link between lysosomal disorders and neurodegenerative diseases. Also, if heterozygous NPC1/2 mutation carriers develop AD we assume it would be worth trying with miglustat-specific therapy recommended for NPC disease.
authors.affiliation: Neurology Clinic, CCS, School of Medicine, University of Belgrade, Dr Subotića starijeg 6, 11000 Belgrade, Serbia.
authors.forename: Nikola
authors.initials: N
authors.lastname: Kresojević
authors.affiliation: Neurology Clinic, CCS, School of Medicine, University of Belgrade, Dr Subotića starijeg 6, 11000 Belgrade, Serbia.
authors.forename: Valerija
authors.initials: V
authors.lastname: Dobričić
authors.affiliation: Neurology Clinic, CCS, School of Medicine, University of Belgrade, Dr Subotića starijeg 6, 11000 Belgrade, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Svetel
authors.affiliation: Neurology Clinic, CCS, School of Medicine, University of Belgrade, Dr Subotića starijeg 6, 11000 Belgrade, Serbia. Electronic address: vladimir.s.kostic@gmail.com.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kostić
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D003704:Dementia / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005962:Glucosylceramidase / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000235:genetics*; D012307:Risk Factors; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; C104585:NPC2 protein, human; D000077296:Niemann-Pick C1 Protein; D033921:Vesicular Transport Proteins; D005962:Glucosylceramidase