CD2AP in Alzheimer's Disease
The age-related dysfunction of the brain is a deep, complicated, and incompletely understood field of study. Even if aging is driven by relatively simple processes of damage, the brain is a very complex organ, and thus the outcome of even simple dysfunctions will be a very complex web of further interacting consequences. Thus there are any number of papers similar to the one noted here, in which researchers focus on one specific protein and what is known of its interactions in the brain. As a rule, discoveries regarding disease-specific mechanisms are usually broadly true, but it is rarely clear (or even easily understood) as to how much these mechanisms contribute to the overall burden of pathology, whether they are in fact useful targets to pursue for the development of therapies, or just minor components of the disease as a whole.
CD2AP is expressed throughout the body. Since the identification of the association between CD2AP and Alzheimer's disease (AD), the function of CD2AP in the brain has been attracting more and more attention. The mRNA data from the Allen Brain Atlas suggest that although CD2AP may be expressed at low levels in neurons, it is relatively enriched in highly plastic brain regions such as the hippocampus, cortex, and cerebellum. In addition, high expression of CD2AP was observed in dendritic endosomes of primary cultured mouse neurons and the absence of CD2AP in neurons was shown to cause synaptic damage. Moreover, we recently discovered that CD2AP was expressed at higher levels in microglia compared to neurons in mice and that CD2AP could regulate microglial activation in response to amyloid-β toxicity.
CD2AP is intricately involved in intracellular protein transport and degradation, vesicle trafficking, cell signaling, and cytoskeleton remodeling. As a risk factor for AD, abnormalities in CD2AP in the nervous system may contribute to the pathogenesis of AD through various mechanisms, including influencing the transport and processing of amyloid precursor protein (APP) and thus amyloid-β generation, participating in Tau-mediated neurotoxicity, disrupting synaptic function and vesicle release, modulating microglial activation, and compromising the integrity of the blood-brain barrier. However, the specific molecular mechanisms by which CD2AP participates in these processes have yet to be fully elucidated.