ABCD
1
2NameAlzheimer's
3Epidemiology5m US, 18m WW
4EtiologyAmyloid processing, Tau aggregation
5Monomers, protofibrils, Fibrils - 10-100nm; Filament: 100A
6Thioflavin-T can be used to monitor fibril formation in vitro.
7AB histidine imidazole
8AB40
9AB42
10AB*56 (Lesne et al).
11primary nucleation, secondary fibril surface catalysed nucleation, elongation rate
12ChemistryAB isoelectric point 5.3 (physiological reduction of pH, possibly due to inflammation, may result in AB insolubility)
13pKa of three histidines is 6.7
14PhysiologyCortex vs. hippocampus
15Genes/ProteinsTREM2, APP, alpha-secretase, beta-secretase, gamma-secretase, PSEN (presenilin)
16APP
17PSEN1 (presenilin-1)
18PSEN2 (presenilin-2) - mutations cause AD
19amyloid beta is produced from sequential processing of APP by BACE and gamma-secretase
20amyloid beta sequence: isoaspartate at position 7
21Tottori FAD mutation (D678N) in APP
22apoE, apoJ
23ScalesAdas-Cog, DAD, MMSE, NPI, CDR-SB, iADRS
24PeopleDennis Selkoe
25JournalsAlzheimers Dement
26Arch Neurol
27J Neurosci
28Alzheimers Res Treat
29Nat Rev Neurology
30CompaniesEli Lilly
31Biogen
32Eisai
33Merck
34Roche
35Sanofi
36Abyssinia Biologics
37Prothena
38AbbVie
39
40Elan