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Table 4 Free parameters

From: Simulations of symptomatic treatments for Alzheimer's disease: computational analysis of pathology and mechanisms of drug action

Name Description Biological Range Optimal Value Reference
Slope %Syn Slope of fraction of synapses disappearing/week Max 0.075%/week, on top of neuronal loss 0.004 [94]
Slope %Neuron Slope of neurons eliminated/week Max 0.5%/week, leads to 50% neuron loss in 100 weeks 0.025 [78]
ACh deficit Size of the cholinergic NBasalis deficit Range 5-50% loss 0.175 [41, 95]
5-HT6 effect Relation between 5-HT6 inhibition and
free DA, ACH and
NE increase
Maximum 0.20 0.025 [33]
DA increase in 12 wk placebo DA surge from reward circuit that simulates placebo effect Maximal 20% (tracer displacement in volunteers) 0.075 [42, 96]
Rel α 7 vs. α 4β 2 nACh-R effect Relative effect of α7 over α 4β 2 nACh-R
mediated effects
Depends upon dose and nature of enhancement Range 0.4-2.0 2 [97]
AChE-I effect on M1 receptor activation AChE-I increases M1 mACh-R activation level to make pyramidal cells more excitable Maximal change in membrane resting potential -8 mV (depolarizing) 0.075/8 mg Gal or equiv [98]
  1. List of 7 free parameters that were calibrated using the relation between clinical outcomes and working model outcomes. We report also the neurophysiological implementation and the biologically realistic boundaries, together with the value determined for the optimal correlation. With these 7 parameters on a database of 28 individual data points we achieve a correlation of r2 = 0.73.