BDNF and Alzheimer disease: These findings, in conjunction with in vitro and in vivo pre-clinical studies, have propelled researchers to speculate that early in the AD disease process, BDNF expression may be upregulated in a “last attempt” to rescue the brain from AD pathology; however, as the disease progresses, the widespread pathology and neurodegeneration associated with AD may ultimately result in the decreased expression of BDNF [31,70,128,129,130,131,132,133,134].