Elimination of the class a scavenger receptor does not affect amyloid plaque formation or neurodegeneration in transgenic mice expressing human amyloid protein precursors

The class A scavenger receptor (SR) is expressed on reactive microglia surr ounding cerebral amyloid plaques in Alzheimer's disease (AD). Interactions between the SR and amyloid beta peptides (A beta) in microglial cultures el icit phagocytosis of A beta aggregates and release of neurotoxins. To asses s the role of the SR in amyloid clearance and A beta-associated neurodegene ration in vivo, we used the platelet-derived growth factor promoter to expr ess human amyloid protein precursors (hAPPs) in neurons of transgenic mice. With increasing age, hAPP mice develop AD-like amyloid plaques. We bred he terozygous hAPP (hAPP(+/-)) mice that were wild type for SR (SR+/+) with SR knockout (SR-/-) mice. Crosses among the resulting hAPP(+/-)SR(+/-) offspr ing yielded hAPP(+/-) and hAPP(-/-) littermates that were SR+/+ or SR-/-. T hese second-generation mice were analyzed at 6 and 12 months of age for ext ent of cerebral amyloid deposition and loss of synaptophysin-immunoreactive presynaptic terminals. hAPP(-/-)SR(-/-) mice showed no lack of SR expressi on, plaque formation, or synaptic degeneration, indicating that lack of SR expression does not result in significant accumulation of endogenous amyloi dogenic or neurotoxic factors. In hAPP(+/-) mice, ablation of SR expression did not alter number, extent, distribution, or age-dependent accumulation of plaques; nor did it affect synaptic degeneration. Our results do not sup port a critical pathogenic role for microglial SR expression in neurodegene rative alterations associated with cerebral beta amyloidosis.