Sex-Related Differences in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to cognitive deficits, functional impairment as well as behavioral changes. The pathophysiology of AD involves the accumulation of neurotoxic amyloid beta protein (A$β$), in early phases, inducing inflammatory and microglial cascades, mitochondrial dysfunction and oxidative stress. These processes then lead to hyperphosphorylation of the microtubule stabilizing protein tau and formation of neurofibrillary tangles. These changes cause synaptic and neuronal dysfunction by disruption of intracellular signaling and widespread cortical dysfunction. Accumulation of amyloid plaques and neurofibrillary tangles further disrupt synaptic integrity and result in neuronal cell death. Despite these well-defined neuropathological hallmarks, human and animal models demonstrate that amyloid plaque burden and distribution do not correlate with cognitive deficit. Neurofibrillary tangles can exist without neuronal impairment, and it is the synaptic loss and network dysfunction that are thought to be related to cognitive deficit [1--4].