1. Genomics
1.1. Gene Silencing
1.1.1. Tau
1.1.1.1. UCL:
1.1.1.1.1. oligonucleotide RNA based therapy
1.1.1.1.2. doseable + reversible
1.1.1.1.3. silence MAPT: tau production
1.1.2. Amyloid Beta 42
1.2. CRISPR/CAS9
1.2.1. Analysis
1.2.1.1. APOE4 (toxic) to APOE2 or APOE3
1.2.1.2. non-viral vector > viral vector [immune response]
1.2.1.3. off target transfection
1.2.2. Tools
1.2.2.1. Knock out genes
1.2.2.1.1. mutant PSEN1 gene: reduced Ab42/Ab40 ratio
1.2.2.2. Knock in genes
1.2.2.3. Gene alterations
1.2.2.3.1. Point mutations
1.2.2.4. Selective gene activation or repression
1.2.2.5. Epigenetic modifications
1.2.3. Currently tested genes
1.2.3.1. APP
1.2.3.2. PSEN1
1.2.3.3. APOE4
1.3. Gene Therapy
1.3.1. extra copy of NF-alpha-1
2. Hallmarks
2.1. Amyloid Beta protein
2.1.1. Pathways
2.1.1.1. Non-amyloidogenic
2.1.1.2. Amyloidogenic
2.1.2. Genes
2.1.2.1. APP
2.1.2.2. PSEN1 and PSEN2
2.1.2.3. APOE
2.1.2.3.1. APOE e4
2.1.2.3.2. APOE e2
2.1.2.3.3. APOE e3
2.1.2.4. BACE1
2.2. Tau Protein (phosphorylated)
2.2.1. Genes
2.2.1.1. MAPT
2.3. Neuroinflammation
2.3.1. receptor: TREM2; ligand: APOE
2.3.2. microglia