Role in Alzheimer's disease In Alzheimer's disease,<unk>  in the brain tissue decreases tremendously, starting in the early stages of the disease. In the mild stages of Alzheimer's disease, the loss of<unk>  can be up to 50% in the white matter and up to 90% in the gray matter in the brain.<unk>  concentration in the cerebral spinal fluid is also lower in subjects with Alzheimer's disease. The characteristic loss of neuronal function associated with Alzheimer's disease occurs via the loss of neurons and synapses, and the deficit is lipid class specific to<unk> s. When comparing<unk>  depletion to other neurodegenerative diseases, Alzheimer's disease is the only case in which<unk>  is so dramatically depleted; in dementia no marked<unk>  depletion is observed, while in Parkinson's disease,<unk>  levels are dramatically elevated, and multiple sclerosis patients only have a moderate<unk>  depletion. Additionally, the loss of<unk>  has been observed to only occur at the very beginning of the disease while at more severe stages, minimal additional<unk>  loss occurs. apolipoprotein E<unk> s in brain tissue has been studied by looking at apolipoprotein E (apoE), specifically the ε4 allele. The ε4 allele of apolipoprotein E is the only known genetic risk factor to significantly indicate late onset Alzheimer's disease. Possessing the apoE ε4 allele has been associated with a higher risk of developing Alzheimer's disease. ApoE is a protein that is involved in the transport of many lipids, including cholesterol, and thus, regulates how much<unk>  is in the central nervous system and mediates the homeostasis of the system. It has been found that higher levels of apoE are positively correlated with greater<unk>  depletion. ApoE-associated proteins take<unk>  from the myelin sheath and then degrade<unk>  into various compounds, such as sulfate. When apoE is increased, the amount of<unk>  that is taken from the myelin sheath is also increased; hence, there is more<unk>  depletion.<unk>  is also involved in the clearance of amyloid-β peptide. Amyloid-β peptides are one of the hallmarks of Alzheimer's disease. When they are not degraded properly, these peptides accumulate and create plaques, which are clumps of amyloid-β peptide pieces, and they are highly associated with Alzheimer's disease. Amyloid-β peptide clearance is important so that this accumulation does not occur.<unk>  facilitates amyloid-β peptide removal through an endocytotic pathway, so when there are high levels of<unk> , there are lower amounts of amyloid-β peptides. Since subjects with Alzheimer's disease have lower<unk>  levels, the clearance of amyloid-β peptides is lower, which allows the peptides to accumulate and create plaques in the brain. Relationship to vitamin K Vitamin K has been found to be associated with<unk> . Not only in animals, but also in bacteria, vitamin K has been observed to influence<unk>  concentrations in the brain. Vitamin K in the nervous system is responsible for the activation of enzymes that are essential for the biosynthesis of brain phospholipids, such as<unk> . When warfarin, a vitamin K antagonist, is added to an animal model system,<unk>  synthesis is impaired. However, when vitamin K is added back into the system,<unk>  synthesis proceeds normally, suggesting that Vitamin K is necessary for<unk>  synthesis.
Sulfatide
Ioxaglic acid
Celadrin 
Gadoteric acid
Co-codaprin
Drotrecogin alfa
Mucrocetin
Ecallantide