The genetic landscape of Alzheimer disease: clinical implications and perspectives.
Antwerp, Belgium. In Genet Med, 27 Sep 2015
It started from the discovery of fully penetrant mutations in Amyloid precursor protein, Presenilin 1, and Presenilin 2 as a cause of autosomal dominant AD, the identification of the ɛ4 allele of Apolipoprotein E as a strong genetic risk factor for both early-onset and late-onset AD, and evolved to the more recent detection of at least 21 additional genetic risk loci for the genetically complex form of AD emerging from genome-wide association studies and massive parallel resequencing efforts.
Cholesterol and metal ions in Alzheimer's disease.
Ann Arbor, United States. In Chem Soc Rev, Nov 2014
For example, (a) cholesterol has been shown to be misregulated in AD-afflicted brains, and the aberrant activity of proteins (particularly, apolipoprotein E (ApoE) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)) has been linked to cholesterol-related AD exacerbation; (b) dyshomeostasis of metal ions associated with misfolded proteins (i.e., amyloid-β (Aβ) aggregates) found in the brains of AD patients is shown to promote oxidative stress leading to the malfunction of multiple proteins, including cytochrome c oxidase (CcO), and Cu/Zn superoxide dismutase (SOD1); (c) metal ion misregulation has also been observed to disrupt the activity of proteins (e.g., HMGR, low-density lipoproteins (LDL)), required for cholesterol production and regulation.
Rockville, United States. In Unknown Journal, 0001
OBJECTIVE: We assessed four pharmacogenetic tests: 1) cytochrome P450, subfamily IIC, polypeptide 9 (CYP2C9), 2) vitamin K epoxide reductase subunit protein 1 (VKORC1), 3) apolipoprotein E (Apo E), and 4) methylenetetrahydrofolate reductase (MTHFR) for their associations with patient’s response to therapy with warfarin (CYP2C9 and VKORC1), statins (Apo E), or antifolate chemotherapy (MTHFR).