7. Blood-based biomarkers Potential sources Platelets Small,
anuclear fragments derived from megakaryocytes in the bone marrow
Platelets Respond to neurotransmitters Enzymes responsible for
generating the A peptide. High concentration of amyloid precursor
protein (APP)
8. Methodology for identifying Biomarkers Validation of
Cooccurrence of other pooled analyte changes consistent with
previous biomarker studies Platelet isolation and membrane protein
enrichment Quantification of membrane-enriched proteome
10. Current drug targets To improve cognitive function Inhibit
acetylcholinesterase (AChE) N-methyl-D-aspartate receptor
11. Novel cognitive-enhancing therapeutic strategies To slow
disease progression in AD patients To enhance cognitive
function
12. Potential Drug Targets Metabotropic glutamate receptor
subtype 5 Increasing the activation of mGlu5 Nicotinic
acetylcholine receptor Activation of the 7nAChR subtype with
smallmolecule agonists M1 Muscarinic acetylcholine receptors
potential to affect multiple disease pathologies including
amyloid-beta and phosphorylated tau
13. Potential Drug Targets Indirect cholinergic
5Hydroxytryptamine stimulation through 5-hydroxytryptamine
receptors (5-HT) receptors 6 Norepinephrine Noradrenergic neurons:
vulnerable during aging Cyclic adenosine monophosphate cAMP
signaling is increased with aging
