In addition, the results of Tanzi and colleagues suggest a potential therapeutic approach

to increasing adult neurogenesis in AD by raising sAPPα levels via gene therapy or direct infusion of sAPPα into the hippocampus. Finally, the current study strengthens the causal link between abnormal Aβ metabolism and LOAD. The hypothesis that LOAD is caused by cerebral Aβ accumulation has been controversial, in part because rare highly penetrant LOAD mutations that affect Aβ metabolism have not been found, unlike the case for EO-FAD. Now, the rare highly penetrant LOAD mutations in the ADAM10 prodomain strongly support the conclusion that there is no qualitative difference between Selleckchem Dinaciclib EO-FAD and LOAD and that they share a similar disease mechanism involving early cerebral Aβ accumulation but that they quantitatively differ in onset and severity depending on the rate of Aβ accumulation. In other words, EO-FAD and LOAD are the same disease but reside in different regions along a pathogenic continuum. As such, the work of Tanzi and colleagues represents an important paradigm shift in the field and further supports the amyloid cascade hypothesis of AD. “
“Alzheimer’s

disease (AD) is pathologically characterized Y-27632 purchase by the presence of both extracellular Aβ deposits and intracellular deposits of tau in the brain. Multiple lines Bay 11-7085 of evidence indicate that accumulation and aggregation of both proteins plays a pivotal role in disease, and thus both Aβ and tau have been the primary foci of efforts to develop disease-modifying therapies for AD. Tau inclusion pathology also is the primary pathological hallmark of several other neurodegenerative disorders such as progressive supranuclear palsy and Pick’s disease. In addition, mutations

in tau that result in neurofibrillary pathology and neurodegeneration can cause FTLD-17t. Thus, tau is a major therapeutic target in AD and in neurodegenerative diseases that are collectively referred to as tauopathies. Following the pioneering preclinical studies by Schenk and colleagues demonstrating the preclinical efficacy of active and passive immunotherapy targeting Aβ, there has been increasing interest in developing immunotherapies to treat AD and other neurodegenerative proteinopathies including human tauopathies. Though many questions remain regarding mechanisms of action of anti-Aβ immunotherapies and optimal trial design to evaluate efficacy in humans, there has been rapid advancement of these therapies into human trials (Golde et al., 2009), although initial therapeutic trials have not shown significant evidence for efficacy in humans with mild to moderate AD (Golde et al., 2011).