Focused ultrasound as a novel strategy for Alzheimer disease therapeutics
There is an urgent need to develop novel and effective treatments for Alzheimer disease (AD). Despite decades of advances in genetics and imaging, we are no further in influencing its inexorable decline to functional dependence and death. Much of the challenge stems from the underlying pathology of AD, which implicates a broad range of neurochemical, cerebrovascular, metabolic, and inflammatory pathways. Our current understanding of AD pathophysiology is centered on the amyloid cascade hypothesis, marked by an accumulation of extracellular amyloid beta (Aβ) plaques and intracellular tau neurofibrillary tangles.1 Aβ oligomers can impair action potentiation, trigger synaptic dysfunction and inflammation, and influence axonal degeneration through hyperphosphorylation of microtubular tau.2 Other histopathologic features include accumulation of neurofibrillary tangles and degeneration of cholinergic neurons in the basal forebrain. Neurofibrillary tangles, composed of the microtubule‐associated protein tau, may be triggered by Aβ plaques, and are strongly correlated with neuronal loss and cerebral atrophy.4 The extent of cholinergic dysfunction is also associated with the degree of cognitive impairment and amyloid plaque load.5 Accordingly, preventing the buildup of beta amyloid, or facilitating its clearance, has become an important target for AD therapeutics.