Table 2.

Summary of studies examining the role of the peripheral immune system on Alzheimer’s disease (AD) pathology. Recent experiments utilizing models of parabiosis and plasma transfers are beginning to address the role of and the extent to which the peripheral immune system and soluble plasma factors may be manipulated in modifying AD pathology and cognition. (↑ = “elevated,” ↓ = “reduced”)

Study	Strain	Age(s)	Model	Duration	Notable Findings
[150]	APP on C57Bl/6 background	Young 2–3 m Aged 16–20 m	Heterochronic parabiosis Aged APP—Young WT Aged APP—Aged APP Aged WT—Aged WT	5 weeks	In the hippocampus: rejuvenation of synaptophysin and calbindin immunoreactivity; no change in total Aβ or Aβ-42 levels; no effect of CD68 immunoreactivity
			Plasma transfer PBS Young plasma	Administration twice weekly for 4 weeks	In the hippocampus: rejuvenation of synaptophysin and calbindin immunoreactivity; no effect of CD68 immunoreactivity Improved memory, spatial learning memory with young plasma transfer
[151]	APPswe/PS1dE9 Tg	Young 3 m Tg 3 m	Heterochronic parabiosis Young Tg—Young WT Age-matched Tg Age-matched WT	6 months	In heterochronic Tg parabionts: ↓ Aβ-40, Aβ-42, total Aβ, and Congo Red plaques in brain ↓ CAA vessel number and area Alleviation of neuronal degeneration and apoptosis
[152]	B6.CD45.1 5XFAD (CD45.2)	4 or 8 m	Parabiosis B6.CD45.1–5XFAD	4 weeks	No recruitment of CD45.1 WT monocytes to brains of 5XFAD parabionts Brain-resident microglia associate with amyloid plaques, not peripheral monocytes
	B6.CD45.1 APP-PS1 (CD45.2)	3.5 m	Parabiosis B6.CD45.1–APP-PS1	9 weeks	No recruitment of CD45.1 WT monocytes to brains of APP-PS1 parabionts