Table 1.
Interaction among different species of Aβ aggregates (f: fibrillar; o: oligomeric; m: monomeric; *: unknown), receptors in NVU cells, and pathological effects.
| Aβ Receptor and Ligand | NVU Cells | Pathological Effects | Ref. |
|---|---|---|---|
| CR1 (CD35) fAβ | Microglia, astrocytes, neurons | fAβ/CR1 interaction results in C3b/C4b activation. Aβ clearance from the brain via blood cell expresses CR1 in its surface and later metabolism in the liver and/or spleen. | [70,71] |
| CR3 (Mac-1) fAβ | Microglia | Interaction leads to an increased PI3K/p47PHOX activity (neurotoxicity by superoxide) or NF-kB (inflammatory factors production). | [72,73] |
| TLR4/6 fAβ | Microglia, astrocytes | CD36/TLR4/6 complex mediates Aβ internalization, followed by ROS and proinflammatory production and phagocytosis. | [74,75] |
| C5aR (CD88) fAβ, oAβ | C5a/C5aR binding in response to fAβ/oAβ induces TNFα production. | [76,77] | |
| SRA 1/2 fAβ, oAβ |
Aβ/SRA interaction results in NF-kB activation and consequently, the secretion of ROS, TNF-a, complement components, among other pro-inflammatory substances. | [78,79] | |
| SRB2 (CD36) fAβ, oAβ | Microglia, BECs, neurons | CD36/a3b1-integrin/CD47 complex regulates fAβ interaction in microglia cells and triggers ROS production, pro-inflammatory cytokines release, and phagocytosis. | [79,80] |
| RAGE mAβ, fAβ | Aβ/RAGE/p38 and ERK1/2 signaling pathways trigger oxidative stress, NF-kB activation, proinflammatory molecules production, triggering NVU damage. | [81,82] | |
| a7nAChR mAβ, fAβ | Neurons, SMCs, astrocytes | a7nAChR may mediate Aβ internalization. Aβ could activate the JNK/ERK2/MAPK pathway, which results in cell death by apoptosis. | [83,84] |
| IR mAβ, oAβ | neurons | Aβ/IR binding triggers impaired insulin signaling, which could cause neuronal dysfunction and memory deficits. | [85,86] |
| SEC-R mAβ | Neurons, glia | Interaction mediates endocytosis and degradation of Aβ by recognizing its 25–35 region. | [87,88] |
| TREM2 oAβ | Microglia, neurons | Decreased TREM2 leads to Aβ accumulation. TREM2/Aβ linking could trigger neuronal phagocytosis or apoptosis. | [89,90] |
| LRP1 mAβ | Pericytes, astrocyte, microglia, neurons | LRP1 is widely expressed in NVU cells and mediates the Aβ transport across the BBB. LRP1 controls the Aβ uptake and its subsequent trafficking to the lysosome for degradation. | [91,92] |
| ABCA1 * Aβ | BECs, pericytes | ABCA1/ApoE/LRP1 complex contributes to brain Aβ transport/clearance. Abca1 gene deficiency promotes Aβ accumulation in an AD mice model. | [93] |
| ABCB1 * Aβ | ABCB1/LRP1 transports the Aβ peptides across the BBB. ABCB1 is considered a marker for BBB maturity and functionality. | [94] |
Abbreviations: ABCA1, ATP binding cassette A1; ABCB1, ATP-binding cassette sub-family B member 1; ApoE, Apolipoprotein E; BBB, blood-brain barrier; BECs, brain endothelial cells; CR, complement receptor; Cx, complement receptor; fAβ, filamentous Aβ; IR, insulin receptor; LRP1, low-density lipoprotein receptor-related protein 1; NF-kB, nuclear factor-ΚB; NVU, neurovascular unit; oAβ, oligomeric Aβ; p47PHOX, neutrophil cytosol factor 1; PI3K, phosphatidylinositol 3-kinase; ROS, reactive oxygen species; SEC-R, serpin-enzyme complex receptor; SMCs, smooth muscle cells; SRA, Class A scavenger receptor; SRB2, scavenger receptor class B member 2; TLR, Toll-like receptor; TREM2, triggering receptor expressed on myeloid cells 2.