Notably, Madsen et al. (2011) observe cerebral 5-HT4 receptor up-regulation starts at a preclinical stage of dementia and it continues while dementia is still at a mild stage and these authors speculate that this upregulation may be a compensatory effect of decreased levels of interstitial 5-HT, increase acetylcholine release or to counteract Aβ accumulation and improved cognitive function. Here, HTR5A is linked to dementia.