VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice.

Although these did not reach statistical significance, there was a strong upward trend in the KO + TLQP-21 vs KO comparison that are absent from the KO + C3aSA vs KO comparison in levels of Wasf1 (logFC = 1.936739127; p -value = 2.50E-05; adjusted p -value = 0.146110951), Dmrtb1 (logFC = 2.907497541; p -value = 2.45E-05; adjusted p -value = 0.146110951) and Adcyap1r1 (logFC = 3.114420357; p -value = 3.40E-05; adjusted p -value = 0.146110951).

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Lack of a significant decrease in amyloid plaque load in TLQP-21-treated 5xFAD females was surprising, despite an observed trend, but could reflect more aggressive amyloid deposition at younger ages in female compared to male 5xFAD mice [ 34 ], which was also observed in APP/PSEN1 mice [ 101 ].

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