<P> In the decade 2002--2012, 244 compounds were assessed in Phase I, Phase II, or Phase III trials, and only one of these (memantine) received FDA approval (though others were still in the pipeline). Solanezumab failed to show effectiveness in patients who already had Alzheimer's symptoms . </P> <P> One area of clinical research is focused on treating the underlying disease pathology . Reduction of beta - amyloid levels is a common target of compounds (such as apomorphine) under investigation . Immunotherapy or vaccination for the amyloid protein is one treatment modality under study . Unlike preventative vaccination, the putative therapy would be used to treat people already diagnosed . It is based upon the concept of training the immune system to recognise, attack, and reverse deposition of amyloid, thereby altering the course of the disease . An example of such a vaccine under investigation was ACC - 001, although the trials were suspended in 2008 . Another similar agent is bapineuzumab, an antibody designed as identical to the naturally induced anti-amyloid antibody . However, immunotherapeutic agents have been found to cause some concerning adverse drug reactions, such as amyloid - related imaging abnormalities . Other approaches are neuroprotective agents, such as AL - 108, and metal - protein interaction attenuation agents, such as PBT2 . A TNFα receptor - blocking fusion protein, etanercept has showed encouraging results . </P> <P> In 2008, two separate clinical trials showed positive results in modifying the course of disease in mild to moderate AD with methylthioninium chloride, a drug that inhibits tau aggregation, and dimebon, an antihistamine . The consecutive phase - III trial of dimebon failed to show positive effects in the primary and secondary endpoints . Work with methylthioninium chloride showed that bioavailability of methylthioninium from the gut was affected by feeding and by stomach acidity, leading to unexpectedly variable dosing . A new stabilised formulation, as the prodrug LMTX, is in phase - III trials (in 2014). </P> <P> Preliminary research on the effects of meditation on retrieving memory and cognitive functions have been encouraging . A 2015 review suggests that mindfulness - based interventions may prevent or delay the onset of mild cognitive impairment and Alzheimer's disease . </P>

The neurodegeneration of alzheimer’s disease starts in which of the following brain regions