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.
Highlights
Alzheimer’s disease (AD), the most common form of dementia, is characterized by the extracellular deposition of parenchymal β-amyloid (Aβ), intracellular accumulation of tau as neurofibrillary tangles (NFTs), synaptic loss, and significant inflammation [1,2]
It has been suggested that perivascular macrophages (PVM) requires the C-C chemokine receptor type 2 (CCR2), a receptor involved in the regulation of macrophage migration and infiltration, to remove amyloid from the brain, since APPswe CCR2−/− mice showed a drastic impairment in Aβ clearance and amplified Cerebral amyloid angiopathy (CAA) [135]
Tau pathology and neuroinflammation have been identified as major contributors of neurodegeneration associated with amyloid deposits in AD and AD-related dementias
Summary
Alzheimer’s disease (AD), the most common form of dementia, is characterized by the extracellular deposition of parenchymal β-amyloid (Aβ), intracellular accumulation of tau as neurofibrillary tangles (NFTs), synaptic loss, and significant inflammation [1,2]. It has been proposed that the amyloid is derived from neurons and is drained along the perivascular interstitial fluid pathway of the brain parenchyma and leptomeninges, depositing along the vessels [10,11] This perivascular drainage impairment sets in motion a self-reinforcing pathway by which worsening vascular amyloid accumulation leads to the activation of vascular injury pathways. We will summarize the existing evidence regarding the amyloid diversity in CAA and its relation to tau pathology and neuroinflammation, as well as discuss the possible contribution of molecular and cellular mechanisms, previously associated with parenchymal amyloid, to the pathogenesis of CAA
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