The Amyloid-Tau-Neuroinflammation Axis in the Context of Cerebral Amyloid Angiopathy

Abstract

Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with the accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis has been associated with an active immune response and perivascular deposition of hyperphosphorylated tau. Despite the fact that in Alzheimer's disease (AD) a major focus of research has been the understanding of the connection between parenchymal amyloid plaques, tau aggregates in the form of neurofibrillary tangles (NFTs), and immune activation, the contribution of tau and neuroinflammation to neurodegeneration associated with CAA remains understudied. In this review, we discussed the existing evidence regarding the amyloid diversity in CAA and its relation to tau pathology and immune response, as well as the possible contribution of molecular and cellular mechanisms, previously associated with parenchymal amyloid in AD and AD-related dementias, to the pathogenesis of CAA. The detailed understanding of the "amyloid-tau-neuroinflammation" axis in the context of CAA could open the opportunity to develop therapeutic interventions for dementias associated with CAA that are currently being proposed for AD and AD-related dementias.

Keywords: amyloid; cerebral amyloid angiopathy; neuroinflammation; tau.

Figure 1

The amyloid-tau-neuroinflammation axis in the context of cerebral amyloid angiopathy (CAA). Amyloid accumulates in the vasculature, causing a destabilization of the neurovascular unit, translated in endothelial damage, pericyte decay, and perivascular macrophage, astrocyte, and microglial reaction. These series of events leads to neuroinflammation. Additionally, tau aggregates in astrocytes and neurons could contribute to neuroinflammation and neurodegeneration observed in CAA. A number of immune-related genes previously associated with AD and the inclusion of tau-related events could be signaled as possible therapeutic targets and a useful tool to contain the detrimental consequences of CAA.