This is most likely why they have the reasoning be

This is most likely why they have the reasoning behind Alzheimer's wrong.

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There is growing evidence that AD is a neuroinflammatory disease characterized by the increased presence of activated microglial cells and astrocytes in the brain (1). Both of these cells generate inflammatory mediators, such as complement proteins, cytokines, and chemokines in response to the Aβ peptide . Because peripheral blood monocytes can cross the blood-brain barrier (BBB) and undergo differentiation into microglial cells , we sought to determine the molecular basis of how peripheral blood monocytes/macrophages may accumulate in the AD brain in response to increased presence of amyloid peptide in circulation and in the brain of AD patients. In our previous studies , we showed that both the soluble (Aβ1–40) and fibrilar (Aβ1–42) form of amyloid peptides could induce the transmigration of human monocytes across cultured brain endothelial cell monolayer, a model of BBB.

Immunohistochemical studies show increased presence of chemokine macrophage inflammatory protein (MIP)-1β in a subpopulation of reactive astrocytes and MIP-1α in neurons of AD brain than those of controls. Moreover, their studies showed that chemokine receptor (CCR)3 and -5 are present on microglial cells of both control and AD brain but with an increased expression on reactive microglia in AD. Because CCR5 is expressed on monocytes and certain lymphocytes, and is activated by the β-chemokines [MIP-1β, MIP-1α, and regulated on activation normal T-expressed and presumably secreted (RANTES)] , we hypothesized that the increased expression of CCR5 on microglial cells or their precursors (monocytes/macrophages) could occur as a result of activation by Aβ peptides.
[url=https://journals.physiology.org/doi/full/10.1152/ajpcell.00461.2004
]https://journals.physiology.org/doi/full/10.1152/ajpcell.00461.2004
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(1) We observed that Aβ peptides at pathophysiological concentrations (125 nM) increased CCR5 mRNA and cell surface protein expression. The cellular signaling involved activation of c-Raf, ERK-1/ERK-2, and c-Jun NH2-terminal kinase. Analysis of some transcription factors associated with CCR5 promoter revealed that Aβ increased DNA binding activity of Egr-1 and AP-1.
https://journals.physiology.org/doi/full/10.1...1.2004#R20

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They say that amyloid peptides increase inflammatory factors and CCR5 expression. But that's putting the cart before the horse. As shown below activation of CCR5 and the accompanying inflammatory factors reduces the clearance of those tau and amyloid plaques.

The overexpression of that CCR5 does not even have to start in the brain or the central nervous system. Increased CCR5 can loosen the tight binds of the blood brain barrier to allow CCR5 expressing cells through to the brain. That exterior CCR5 could be caused by any number of factors, viruses, genetic mutations not directly related to CCR5, other disease states or simply ageing.

So what do we know about how high levels of CCR5 and inflammatory factors can damage the brain. We know overreactive microglia can damage the neuoronal sheath and kill the neurons themselves. We know it can lead to dendritic spine loss. They suppress cortical plasticity. They increase oxidative stress leading to a loss of synaptic function. Which of course leronlimab can reverse.

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We found that the microglial-derived CCL-3/-4/-5 bind and activate neuronal CCR5, which in turn promotes mTORC1 activation and disrupts autophagy and aggregate-prone protein clearance. CCR5 and its cognate chemokines are upregulated in the brains of pre-manifesting mouse models for Huntington’s disease (HD) and tauopathy, suggesting a pathological role of this microglia-neuronal axis in the early phases of these diseases. CCR5 upregulation is self-sustaining, as CCL5-CCR5 autophagy inhibition impairs CCR5 degradation itself. Finally, pharmacological or genetic inhibition of CCR5 rescues mTORC1 hyperactivation and autophagy dysfunction, which ameliorates HD and tau pathologies in mouse models.
[url=https://www.cell.com/neuron/fulltext/S0896-6273(23)00268-4
]https://www.cell.com/neuron/fulltext/S0896-6273(23)00268-4
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Maraviroc significantly reduced HIV-induced amyloidogenesis, GSAP, phospho-Tau, neurodegeneration, BBB alterations, and leukocytes infiltration into the CNS. Maraviroc increased cellular Aβ efflux and transendothelial Aβ transport via LRP1 pathways. Thus, therapeutically targeting CCR5 could reduce viremia, preserve the BBB and neurons, increased brain Aβ efflux, and reduce AD-like neuropathologies.
https://pubmed.ncbi.nlm.nih.gov/34809709/

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